Effects ofgold salts and prednisolone inflammatory cells · Ann. rheum. Dis. (1973) 32, 294 Effects ofgold salts and prednisoloneon inflammatorycells 1. Phagocyticactivityofmacrophagesandpolymorphsin

Ann. rheum. Dis. (1973) 32, 294

Effects of gold salts and prednisolone oninflammatory cells1. Phagocytic activity of macrophages and polymorphs ininflammatory exudates studied by a 'skin-window' techniquein rheumatoid and control patients

J. D. JESSOP, B. VERNON-ROBERTS, AND JACQUELINE HARRISDepartment ofRheumatology, University Hospital of Wales, Cardiff; Bone andJoint Research Unit, Institute ofPathology, The London Hospital Medical College; and Department ofRheumatology, The London Hospital

Whatever the stimulus to inflammation, for exampletraumatic, bacterial or immunological damage totissues, macrophages and neutrophil polymorphsusually accumulate in large numbers in the inflamedarea, and there is abundant experimental evidencethat these cells originate in the bone marrow(Volkman and Gowans, 1965a, b; Spector andWilloughby, 1968). Inflammation of synovial tissuesis a cardinal feature of rheumatoid arthritis and vari-able numbers of macrophages and polymorphs arepresent within the synovium and synovial fluid inaffected joints. Lysosomal enzymes of the macro-phages and polymorphs present in rheumatoid pan-nus are actively concerned in the destruction ofarticular cartilage (Dingle, 1969; Chayen andBitensky, 1971). In addition to their phagocytic anddigestive role in inflammation, it is now widelyacknowledged that macrophages are probably in-volved in the initial handling of antigens in someimmune responses and are probably involved invarious aspects of cell-mediated immune reactions.In this latter connection, in rheumatoid arthritis, avariety of autoantibodies directed against immuno-globulins and various organs are usually present, andcell-mediated immune reactivity to certain antigenshas been demonstrated (Williams and Bruckner,1971; Berry, Bacon, and Davis, 1972).

Since the activity of macrophages and polymorphsis fundamental to various aspects of rheumatoidarthritis, including the effects of anti-inflammatorytherapy, it would seem likely that a method ofmeasuring the activity of these cells could provideuseful information. Of the known activities of macro-phages and polymorphs, phagocytosis is easilyassessed in the experimental animal. A variety oftechniques have been used to assess phagocytosis inthe human but they are time-consuming and are notsuitable for routine use. We have adapted the 'skin-window' technique of Rebuck and Crowley (1955) to

Accepted for publication December 21, 1972

investigate the phagocytic activity of inflammatorymacrophages and polymorphs in rheumatoid andcontrol subjects.

Methods

ASSESSMENT OF PHAGOCYTIC ACTIVITY BY'SKIN-WINDOW TECHNIQUEAn area of skin on the lateral aspect of either upper armwas swabbed with 'Repelcote' silicone solution (Hopkinsand Williams) which was allowed to dry. A small area ofthe cleaned skin was then lightly scratched with a sterileneedle, any oozing of blood being arrested by pressure,and an 8 mm. diameter glass coverslip (Chance Pilkington)which had been coated previously on one side with a driedlayer of a suspension ofcolloidal carbon (Gunther Wagner,carbon code number C1 1/1431a) was applied to theabraded area. The coverslip was held in place by a circularplaster dressing (Band-Aid 7/8" Spots, Johnson andJohnson) having a 9 mm. diameter central pad. Threecarbon-coated coverslips were applied in this way on eachoccasion. In the inflammatory response which followedthe above procedure, macrophages and neutrophil poly-morphs migrated to the inflamed area and adhered to theglass coverslip. 24 hours after application, the coverslipswere removed, air-dried, fixed by immersion in absolutemethanol for 2 minutes, stained with Giemsa 'R66'(George T. Gurr), and mounted with the cell-free surfaceuppermost. Examination of the stained coverslips re-vealed that the cell population was usually composed ofabout 75 per cent. macrophages and 25 per cent. neutrophilpolymorphs, and a variable proportion ofthese phagocyticcells contained visible aggregates of phagocytosed carbonparticles (Fig. 1, opposite). The precentages of macro-phages and neutrophil polymorphs containing visiblephagocytosed carbon aggregates were assessed by ran-domly selecting and examining a minimum of 300 cells ofeach type on each coverslip using an oil immersionobjective (total magnification 1,000 x).

RELIABILITY OF METHODPreliminary studies using one of us (BVR) as a healthycontrol subject showed that, in repeated estimates of

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Effects ofgold salts andprednisolone on inflammatory cells. I 295

FIG. 1 Macrophages and polymorphs adhering to glass24 hrs after application ofcoverslip. The cytoplasm ofmanycells contains aggregates ofcarbon. Giemsa. x 1,000phagocytic activity carried out at short or prolongedintervals using the above technique, the variation in thenumbers of macrophages and neutrophil polymorphscontaining visible carbon was limited to about 10 per cent.(Fig. 2). Additional evidence for the reliability of thetechnique as a method of measuring phagocytic activitywas provided by parallel studies in experimental animalsgiven anti-inflammatory drugs, which showed a linearrelationship between the percentage of cells containingvisible carbon and the dose of sodium aurothiomalate orprednisolone (Vernon-Roberts, Jessop, and Dore, 1973).

SELECTION, GROUPING, AND CLINICAL

ASSESSMENT OF SUBJECTS

Phagocytic activity was assessed in four groups of sub-jects who were matched for age and sex distribution insofar

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* Macrophages F: PolymorphsFIG. 2 Percentage of macrophages and polymorphs con-taining carbon assessed at short and long intervals in a con-trol subject

as this was possible (Table I). The control group com-prised fifty subjects who were either completely healthy orsuffered from degenerative joint disease alone. The sub-jects in the other three groups were all suffering fromclassic or definite rheumatoid arthritis (Ropes, Bennett,Cobbs, Jacox, and Jessar, 1959), and comprised 61patients (77 per cent. seropositive) not receiving gold saltsor prednisolone, 51 patients (61 per cent. seropositive)receiving gold (sodium aurothiomalate-'Myocrisin',May and Baker), and 31 patients (71 per cent. seropositive)receiving prednisolone. At the time of presentation about80 per cent. of the patients in each of the three groups ofrheumatoid subjects were receiving drugs such as indo-methacin, butazolidine, ibuprofen, paracetamol, or sali-cylates. In these cases, coverslip application was delayeduntil one week after withdrawal of these drugs, or, in thecase of salicylates, until blood salicylate levels had fallento zero. At the time of coverslip application, the rheuma-toid patients were examined and the presence of activeinflammation of the joints was scored on a 0 to 4 scale(0= no inflammation; 4 = severe inflammation). Thepatients' notes were reviewed retrospectively and anassessment was made of the response to gold therapybased on an improvement in the severity of joint inflam-mation and the degree of disability. The tube latex test,haemoglobin, total and differential white cell count, anderythrocyte sedimentation rate was determined in eachcase. In the patients receiving gold therapy, serum gold

Table I Number, age, and sex of control, rheumatoid, gold-treated rheumatoid, and prednisolone-treatedrheumatoid groups of subjects investigated by the 'skin-window' techniquteGroup No. in group Sex Age (yrs)

Male Female Mean (Range)

Controls 50 18 32 46 (20-80)RA 61 27 34 54 (30-82)RA/Gold 51 21 30 52 (19-70)RA/Pred 31 11 20 57 (31-84)



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296 Annals of the Rheumatic Diseases

estimations were carried out using the method of Lorber,Cohen, Chang, and Anderson (1968).

Results

PHAGOCYTIC ACTIVITY OF MACROPHAGESFig. 3 shows that the range of 'scores' for the percent-age of macrophages containing visible carbon was in

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FIG. 3 Percentage of macrophages containing carbon innon-rheumatoid controls, rheumatoids (RA), and rheuma-toids treated with gold (RA/GOLD) and prednisolone(RA/PRED)

the order of 50 per cent. for each of the four groups.The mean score of the non-rheumatoid control groupwas 53 per cent.; the scores in the rheumatoid groupwere generally higher with a mean of 73 per cent.; inthe gold-treated rheumatoids the mean score was45 per cent.; and in the prednisolone-treated rheuma-toids the mean score was reduced to 26 per cent.Analysis of these results (Table II) shows that thesemean scores are all significantly different. Thus, rela-tive to the non-rheumatoid control subjects, thephagocytic activity of macrophages is significantlyraised in rheumatoid arthritis, is suppressed duringtreatment with gold, and is markedly suppressedduring treatment with prednisolone.

In none of the groups was there a significant degreeof correlation between individual macrophage scoresand factors such as age, sedimentation rate, white cellcount, duration of disease, or a crude scored estimateof disease activity. In the gold-treated group, therewas no significant correlation between individualmacrophage scores and serum gold levels on the totaldose of gold which each patient had received. How-ever, those patients who had exhibited a definitebeneficial response to gold had a significantly lowermean macrophage score than those patients in whoma beneficial response was absent (Table III).

PHAGOCYTIC ACTIVITY OF NEUTROPHILPOLYMORPHSFig. 4 shows that the percentage of polymorphs con-taining visible carbon were generally appreciablylower in all four groups than was observed in the caseof macrophages (Fig. 3). The range of scores for thepercentages of polymorphs containing visible carbonalso showed greater variation than in the case of

Table II Comparison ofmeans ofpercentage ofmacrophages containing carbon in non-rheumatoid, rheumatoid,gold-treated rheumatoid, andprednisolone-treated rheumatoid subjects

Groups under comparison Probability of significanceofdifference between means

Group Mean + S.E. Group Mean + S.E.

Controls 53 + 2 RA 73 + 2 P < 0 001Controls 53 ± 2 RA/Gold 45 ± 2 P < 001Controls 53 ± 2 RA/Pred 26±2 P <O-OO1RA 73 ± 2 RA/Gold 45 ±2 P<OOO1RA 73 ± 2 RA/Pred 26±2 P<0001RA/Gold 45 ± 2 RA/Pred 26 ± 2 P < 001

Tablem Mean percentage ofmacrophages containing carbon in rheumatoid patients exhibiting apositive ornegative beneficial response to treatment with sodium aurothiomalate

Beneficial response to No. ofcases Percentage ofmacrophages Probability ofsignificance ofchrysotherapy containing carbon (mean ± S.E.) difference between means

Definite response 33 46 3 P < 0.05Doubtful or absent 15 56 ± 3



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FIG. 4 Percentage of polymorphs containing carbon innon-rheumatoid controls, rheumatoids (RA), and rheuma-toids treated with gold (RARGOLD) and prednisolone(RA/PRED)

macrophages, and was least in the prednisolone-treated group (about 20 per cent.) and greatest in thegold-treated group (about 60 per cent.).The mean score of the non-rheumatoid control

group was 24 per cent.; the scores in the rheumatoidgroup were higher with a mean of 37 per cent.; in thegold-treated rheumatoids the mean score was 27 percent.; and in the prednisolone-treated rheumatoidsthe mean score was reduced to 11 per cent. Analysisof these results (Table IV) shows that, relative to thenon-rheumatoid control subjects, the phagocyticactivity of neutrophil polymorphs is significantlyraised in rheumatoid arthritis and is markedly sup-pressed during treatment with prednisolone; al-though the mean phagocytic score of the gold-treatedrheumatoid group was not significantly differentfrom the non-rheumatoid control group, it wassignificantly lower than the mean score of therheumatoid group not receiving gold or prednisolone.As in the case ofmacrophages, there was no signifi-

cant correlation between individual polymorph scores

and such factors as age, sedimentation rate, whitecell count, duration of disease, or a crude scoringestimate of disease activity. In the gold-treated group,there was no significantcorrelation between individualpolymorph scores and serum gold levels or the totaldose of gold which each patient had received.

PHAGOCYTIC ACTIVITY OF MACROPHAGESAND POLYMORPHS DURING GOLD THERAPYIn sixteen of the rheumatoid patients receiving gold,phagocytic activity was assessed at various intervalson two or more (up to five) occasions.Twelve of the sixteen patients receiving weekly

injections of gold exhibited a progressive reduction inmacrophage phagocytic scores during the period ofobservation (intervals of 1 day to 9 months), but thepolymorph scores were variable and did not show auniform pattern ofresponse although a reduction wasobserved in the first few days after gold injection inmany cases. It was generally observed that there wasusually relatively little change detectable in macro-phage scores assessed at daily intervals, and thegreatest reduction in phagocytic activity was usuallyobserved if at least 5 to 7 days were allowed toelapse between phagocytic assessments: this reduc-tion was particularly marked about 5 to 7 days aftereach gold injection. The findings in two of the patientsin this group are illustrated in Fig. 5 (overleaf). Inboth subjects the serum gold levels were elevated24 hours after each gold injection, and fell to lowerlevels 1 week later. In contrast, there was a progressivefall in the percentage of macrophages containingvisible carbon. In patient J.D. the polymorph scoreswere variable; but in patient V.J. the polymorphscores were reduced 24 hours after each gold injection,but had returned to the higher level at the time whenthe next injection was due.

In three of the sixteen patients, there was no ob-served change in macrophage scores. However, one ofthese, who was receiving weekly injections of gold,had only two phagocytic assessments which werecarried out on successive days; and the other twopatients, who were receiving monthly injections ofgold, had three phagocytic assessments carried out at

Table IV Comparison ofmeans ofpercentage ofpolymorphs containing carbon in non-rheumatoid, rheumatoid,gold-treated rheumatoid, and prednisolone-treated rheumatoid subjects

Groups under comparison Probability ofsignificance ofdifference between means

Group Mean ± S.E. Group Mean + S.E.

Controls 24 1 RA 37+2 P<0001Controls 24 1 RA/Gold 27 i1 P> 0-05Controls 24± 1 RA/Pred 11 1 P < 0001RA 37 2 RA/Gold 27 i1 P <0001RA 37 2 RA/Pred 11 i1 P<O01RA/Gold 27 ± 1 RA/Pred 11 ± 1 p < 0-001



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* Macrophages0J Polymorphs

Q Serum gold

2 8 9Days

2 8 9 15

FIG. 5 Changes in serumn gold atid nacrophage andpolymorph phagocytic scores during treatment with weekly injectionis of50 mg. sodilum auirothiomalate (arrows) in two rheumatoidpatients

monthly intervals in one case and 2-monthly intervalsin the other.The remaining patient of the sixteen was also re-

ceiving monlthly injections of gold and showed a re-

duction in macrophage and polymorph scores duringthe first 3 days after injection (Fig. 6). However, im-mediately before the next gold injection 1 monthlater, it was observed that the macrophage and poly-morph scores had returned to the previous high levels.

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FIG. 6 Changes in macrophage andpolymorph phagocyticscores in a rheumatoid patient during the month following a

single 50 mg. injection of sodium alurothiomalate

These repeated assessments of phagocytic activityin rheumatoid patients receiving gold therapy re-

vealed that macrophage phagocytic activity becomesprogressively suppressed during treatment withweekly injections of gold, the greatest incrementalreduction being observed 5 to 7 days after each goldinjection. During treatment with monthly injectionsof gold, an initial fall in macrophage phagocyticactivity is followed 1 month later by a return to thehigher pre-injection level. The phagocytic behaviourof polymorphs during gold therapy is variable, butin many cases a reduction in polymorph scores

was observed during the 3 to 4 days after each goldinjection.

Discussion

Using a modified skin-window technique to assess

phagocytic activity, we have found that the phago-cytic activity of macrophages and neutrophil poly-morphs at inflammatory sites artificially induced inthe skin is elevated in rheumatoid arthritis and sup-

pressed during treatment with gold salts and predniso-lone. This finding of a hyperphagocytic state of theinflammatory cells at extra-articular sites in rheuma-matoid arthritis indicates that, in rheumatoid arth-ritis, there must be present a factor or factorsstimulating phagocytosis generally and these factorsare not confined to the environment of inflamedjoints.

There is morphological evidence of increasedphagocytic and pinocytotic activity in the synovial


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lining cells in rheumatoid joints, indicated by anincrease in the number and length of filopodia and astriking increase in the number of lysosomes(Ghadially and Roy, 1969). There is similar morpho-logical evidence of increased phagocytic and pino-cytotic activity by macrophages and polymorphs injoint effusions in rheumatoid arthritis (Zucker-Franklin, 1966). The question obviously arises as tothe nature of the stimuli to increased phagocyticactivity by phagocytes within rheumatoid joints andwhether such stimuli could also be the cause of theincreased phagocytic activity which we have observedin extra-articular inflammatory sites in patients withrheumatoid arthritis.

It has been suggested that the joint inflammationcharacteristic of rheumatoid arthritis could representan immunopathological response to an exogenousor endogenous constituent present in the joint(Glynn, 1968). Immunoglobulins, rheumatoid factor(RF), and complement components have all beenfound in the intimal cells of the synovium (Rodman,William, Bilka, and Muller-Eberhard, 1967; Bonomo,Tursi, and Gillardi, 1968; Brandt, Cathcart, andCohen, 1968) and within cytoplasmic inclusions ofleucocytes of the synovial fluid (Zucker-Franklin,1966; Vaughan, Barnett, Sobel, and Jacox, 1968)from patients with rheumatoid arthritis. The factthat we have been able to demonstrate the presence ofIgM, IgG, and fl, within macrophages and poly-morphs adhering to skin-window coverslips in rheu-matoid patients (Vernon-Roberts and Jessop, 1972)could suggest that similar immunological factorsmay influence the function of inflammatory cells atextra-articular sites. In the absence of acute inflam-mation, circulating immunoglobulin molecules donot easily diffuse into extravascular fluids (Macka-ness, 1970). However, the trauma and acute inflam-matory response resulting from scratching the skincould feasibly allow the escape of circulatingimmunoglobulins or immune complexes into theinflammatory site, where they could stimulate phago-cytic cells by direct action or indirectly by, for ex-ample, inducing the release of a phagocytosis-stimu-lating factor (Barnet, Pekarek, and Johanovsky,1968) from sensitized lymphocytes.

Prednisolone therapy is consistently effective inreducing inflammation in rheumatoid arthritis andwe have found that it also induces a marked reductionin phagocytic activity below non-RA control level.This marked reduction in phagocytic activity mustpartly account for the increased susceptibility ofprednisolone-treated patients to various infections.Gold salts were more variable in their effects and aresignificantly less potent than prednisolone in suppres-sing rheumatoid inflammation; and it is of interestthat we have found that patients who exhibiteda beneficial clinical response to gold therapy hadsignificantly lower macrophage phagocytic scores

than patients in whom the beneficial response wasabsent.While we could find no significant correlation be-

tween various clinical and laboratory findings andmacrophage and polymorph phagocytic scores,serial observations in patients receiving weekly goldinjections showed that there was a progressive de-cline in macrophage phagocytic scores as treatmentprogressed, indicating that gold salts have a pro-gressive 'saturating' effect on these cells. The lowestlevels of phagocytic activity were usually observed5 to 7 days after each gold injection, and the resultsobtained in a single patient indicated that macro-phage phagocytic activity were restored to pre-injection level within 1 month after the gold injection.While bearing in mind the small number of patients inwhom serial observations were performed, these re-sults are strikingly similar to our findings in rats(Vernon-Roberts and others, 1973).The final and probably most important considera-

tion is whether the coverslip test we have used couldbe of value in the assessment of rheumatoid diseaseactivity or the response of RA patients to anti-inflammatory therapy. The changes in the percent-ages ofcarbon-containing cells on coverslips would bethe result of changes in:

(1) The number of monocytes and neutrophils pro-duced in the bone marrow,(2) The number of cells released from the bonemarrow pool,(3) The migration of cells from the blood into theextravascular inflammatory site,(4) The adherence of the cells to the glass of thecoverslip,(5) Phagocytic activity.

However, there is no doubt that the end-result of theassessment-the phagocytic score-is significantlyelevated in RA and reduced by anti-inflammatorytherapy. These latter findings alone would appear toprovide sufficient reason for the further investigationof the use of this simple technique as a means ofassessing the efficacy of anti-inflammatory drugs andthe response of individual patients to gold andprednisolone therapy. We plan to examine thisaspect by the application of serial coverslips to indivi-dual RA patients before and during anti-inflam-matory therapy and by correlating the findings with adocumentation of clinical and laboratory parameters.

Summary

The phagocytic activity of macrophages and neutro-phil polymorphs in inflammatory exudates wasstudied using a 'skin-window' technique in rheuma-toid and control subjects. The phagocytic activity ofmacrophages and polymorphs was increased inpatients having rheumatoid arthritis when compared



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to non-rheumatoid controls, was suppressed in receiving monthly injections of gold, an initial fall inrheumatoid patients receiving treatment with gold macrophage phagocytic activity in the immediatesalts, and was markedly suppressed in rheumatoid post-injection period was followed by a return to thepatients receiving prednisolone. The mean macro- higher pre-injection levels 1 month later.phage phagocytic score was significantly lower inpatients responding clinically to gold therapy than inthose who failed to respond. A progressive reduction The authors are grateful to Dr. R. M. Mason, Dr. H. L. F.in macrophage phagocytic activity was observed Currey, and Dr. C. G. Barnes of the Department ofduring serial observations in some of the patients Rheumatology, The London Hospital, for permission toreceiving weekly injections of gold. In one patient study their patients.

References

BARNET, K., PEKAREK, J., AND JOHANOVSKY, J. (1968) Experientia (Basel), 24, 948 (Demonstration of specificinduction of erythrocyte phagocytosis by macrophages from normal non-sensitized rabbits by a factor releasedfrom lymph node cells of immunized rabbits)

BERRY, H., BACON, P. A., AND DAVIS, J. D. (1972) Ann. rheum. Dis., 31, 298 (Cell-mediated immunity in Sj6gren'ssyndrome)

BONOMO, L., TURSI, A., AND GILLARDI, U. (1968) Ibid., 27, 122 (Distribution of the anti-gamma globulin factors in thesynovial membrane and other tissues in various diseases)

BRANDT, K. D., CATHCART, E. S., AND COHEN, A. S. (1968) J. Lab. clin. Med., 72, 631 (Studies of immune depositsin synovial membranes and corresponding synovial fluid)

CHAYEN, J., AND BITENSKY, L. (1971) Ann. rheum. Dis., 30, 522 (Occasional survey: Lysosomal enzymes andinflammation)

DINGLE, J. T. (1969) 'The extracellular secretion of lysosomal enzymes', in 'Lysosomes in Biology and Pathology',ed. J. T. Dingle and H. B. Fell, vol. 2, p. 421. North-Holland, Amsterdam

GHADIALLY, F. N., AND Roy, S. (1969) 'Ultrastructure of Synovial Joints in Health and Disease'. Butterworths, LondonGLYNN, L. E. (1968) Ann. rheum. Dis., 27, 105 (Heberden Oration, 1967: The chronicity of inflammation and its

significance in rheumatoid arthritis)LORBER, A., COHEN, R. L., CHANG, C. C., AND ANDERSON, H. E. (1968) Arthr. and Rheum., 11, 170 (Gold

determination in biological fluids by atomic absorption spectrophotometry: application to chrysotherapy inrheumatoid arthritis patients)

MACKANESS, G. B. (1970) 'Cellular immunity,' in 'Mononuclear Phagocytes', ed. R. Van Furth, p. 461. Blackwell, Oxfordand Edinburgh

REBUCK, J. W., AND CROWLEY, J. H. (1955) Ann. N. Y. Acad. Sci., 59, 757 (A method for studying leukocytic functionsin vivo)

RODMAN, W. S., WILLIAM, R. C., BILKA, P. J., AND MULLER-EBERHARD, H. J. (1967) J. Lab. clin. Med., 69, 144(Immunofluorescent localization of the third and fourth component of complement in synovial tissue frompatients with rheumatoid arthritis)

ROPES, M. W., BENNETT, G. A., COBB, S., JACOX, R., AND JESSAR, R. A. (1959) Ann. rheum. Dis., 18, 49 (Revision ofdiagnostic criteria for rheumatoid arthritis)

SPECTOR, W. G., AND WILLOUGHBY, D. A. (1968) J. Path. Bact., 96, 389 (The origin of mononuclear cells in chronicinflammation and tuberculin reactions in the rat)

VAUGHAN, J. H., BARNETT, E. V., SOBEL, M. V., AND JACOX, R. F. (1968) Arthr. and Rheum., 11, 125 (Intracytoplasmicinclusions of immunoglobulins in rheumatoid arthritis and other diseases)

VERNON-ROBERTS, B., AND JESSOP, J. D. (1972) Ann. rheum. Dis., 31, 536 (The effects of gold and prednisolone oninflammation and phagocytosis in the rat)

-, , AND DORE, J. (1973) Ibid., 32, 301 (Effects of gold salts and prednisolone on inflammatory cells. II.Suppression of inflammation and phagocytosis in the rat)

VOLKMAN, A., AND GOWANS, J. L. (1965) Brit. J. exp. Path., 46, 50; 62 (The production ofmacrophages in the rat; Theorigin of macrophages from bone marrow in the rat)

WILLIAMS, M. H., AND BRUCKNER, F. E. (1971) Ann. rheum. Dis., 30, 271 (Immunological reactivity to Mycoplasmafermentans in patients with rheumatoid arthritis)

ZUCKER-FRANKLIN, D. (1966) Arthr. and Rheum., 9, 24 (The phagosomes in rheumatoid synovial fluid leukocytes: alight, fluorescence and electron-microscopic study)



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Documents

Effects ofgold salts and prednisolone inflammatory cells · Ann. rheum. Dis. (1973) 32, 294 Effects ofgold salts and prednisoloneon inflammatorycells 1. Phagocyticactivityofmacrophagesandpolymorphsin