Inhibition by 6-Mercaptopurine of Polyarthritis induced by Freund's Adjuvant

Kalliomäki, J. L.; Saarimaa, H. A.; Toivanen, Paavo

doi:10.1136/ard.23.1.78

Cited by 36 publications

(13 citation statements)

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“…When a purine antagonist, 6-mercaptopurine, was administered to patients with systemic lupus erythematosus the responses were equivocal (Lee, Meiselas, Zingale, and Richman (1961). The development of adjuvant-induced arthritis in rats has been successfully inhibited by 6-mercaptopurine (Kalliomaki, Saarimaa, and Toivanen, 1964). Methotrexate has been used experimentally in psoriatic arthritis (O'Brien, Van Scott, Black, Eisen, and Bunim, 1962; Scott, Auerbach, Eisen, and Bunim, 1964).…”

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confidence: 99%

Evaluation of Intra-Articular Thio-Tepa in Rheumatoid Arthritis

et al. 1966

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Evaluation of Intra-Articular Thio-Tepa in Rheumatoid Arthritis

et al. 1966

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“…Suppression of adjuvant-induced polyarthritis by 6-mercaptopurine has been demonstrated by several groups of investigators (6,14,28). It has not been established, however, whether the drug suppresses adjuvant arthritis by virtue of its immunosuppressive or its antiinflammatory properties, or both.…”

Section: Discussionmentioning

confidence: 99%

“…A causal relationship between suppression of the cell-mediated immune response and suppression of arthritis development has been suggested by Kalliomaki et al (14) and by Perper et a1 (28) based on the observations that the drug brought about a simultaneous inhibition of the development of adjuvant arthritis and delayed dermal hypersensitivity to tuberculin. On the other hand, Ward et al (6) reported that 6-mercaptopurine (25-100 mg/kg IM or IP) suppressed or prevented the development of adjuvant arthritis without altering either the humoral or the cellular hypersensitivity to old tuberculin.…”

Section: Discussionmentioning

confidence: 99%

“…The compound has been shown to suppress the primary humoral immune response in rats ( 1 1 ) and mice (l2,13), and to suppress the development of the cell-mediated immune response in rats (14) and guinea pigs (15), although the effects are highly dependent on experimental conditions and the species of the animals. Santos and Owens ( 1 1) showed that 6-mercaptopurine suppressed the production of antibody to sheep erythrocyte in rats only when the antigen was administered from 2 days before to the second day of the 5-day course of drug treatment.…”

Section: Discussionmentioning

confidence: 99%

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Mechanisms Underlying the Suppression of Adjuvant‐Induced Arthritis by 6‐Mercaptopurine

Chang

1977

Arthritis & Rheumatism

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Daily oral administration of 6-mercaptopurine suppressed the development of the secondary (immune) lesions of adjuvant arthritis in a dose-related manner. The degrees of arthritis suppression corresponded closely to suppressions of concurrent development of the humoral and the cellular immune response to El, cells. A short course of therapy during the sensitization period (day -1 to day 5 when the day of adjuvant injection is designated as day 0) appeared to be almost as effective as continued daily dosing (day -1 to day 15). The drug did not influence the development of the primary (nonimmune) lesions of adjuvant arthritis at all dosage levels investigated. Chronic pretreatment with 10 mg/kg/day PO for 17 days had no effect on the development of carrageenin-induced acute inflammation in the rat. The suppression of adjuvant arthritis by 6-mercaptopurine, unlike suppression by cyclophosphamide, appears to result primarily from its suppressive action on the immune response.6-Mercaptopurine is known to have both immunosuppressive and antiinflammatory properties (1,2). The drug has been shown to suppress adjuvant-induced polyarthritis in the rat, a disease thought to be the result of a delayed hypersensitivity response to bacilli or their components (3,4), presumably by a combination of immunosuppressive and antiinflammatory actions (5,6). This study was undertaken to determine the relative contributions of antiinflammatory and immunosuppressive activities in the suppression of adjuvant arthritis by 6-mercaptopurine. MATERIALS AND METHODSMaintenance of El, Cell Line. The El, tumor cell line was a gift from Dr. J. Wunderlich, NIH, Bethesda, MD. El, cells were maintained by passage in syngeneic C57/bl 6 mice (Jackson Laboratories, Bar Harbor, ME). The cells (2 X lo7)were injected intraperitoneally on day 0. On day 7, approximately 3-5 X 108 cells per mouse were harvested from the peritoneum, and after washing with Hanks' minimum essential medium (HMEM), they were used either for replanting the cell line, for immunization, or as target cells in immune assays.Polyimmune Adjuvant Arthritis. Adjuvant arthritis was produced by a single subcutaneous injection of 1 mg of Mycobacterium butyricum (Difco Laboratories, Detroit, M I ) suspended in 0.1 ml of mineral oil into the right hind paw of male Lewis inbred rats (Microbiological Associates, Bethesda, MD) weighing between 235 and 250 g. A I .O ml suspension of El, cells ( 1 X 108 cells/ml) in HMEM was injected intraperitoneally immediately after the subplantar injection of adjuvant. The paw volume was measured by the method of Winter et al(7) on days 0,4, and 16 (or 22) with respect to the injection of adjuvant. All rats were treated with either saline or drug (PO or IM) daily from day -1 to day + 15 unless otherwise noted. After paw volume was measured on day 16, a sample of blood was taken and the spleen was removed. The serum and spleen cells were used to measure immune response.

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“…However, the exact mechanism of the development of secondary lesions are still uncertain. Reports have shown that the dissemination and processing of adjuvant components is involved in the induction of AA (Kalliomaki et al 1964 ;Newbould 1964;Waksman et al 1960).…”

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Lymphocyte Subsets and Mitogen Induced Proliferation in Adjuvant Arthritis. Part II. Changes in Function and Numbers of Lymph Nodes T Lymphocytes.

Tsai

Liu

1992

Tohoku J. Exp. Med.

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To evaluate the effects of lymphocytes on the pathogenesis of adjuvant arthritis (AA), the lymphocytic responses to phytohemagglutinin (PHA) and concanavalin A (Con A) and the percentages of T cell subpopulations were investigated in the inguinal lymph nodes of Long-Evans (LE) rats and Sprague-Dawley (SD) rats after a single injection of complete Freund's adjuvant. The response of LE to PHA increased to its maximum on the 14th day and correlated with the severity of AA. The responses of LE and SD rats to Con A were decreased on the 7th, 11th, and 14th days. Additionally, percentage of suppressor T cells of LE rats was lower than that of SD rats. Significant increases of percentage of helper T cells and of helper/suppressor T cell ratio were observed in LE rats, indicating a decrease or defect in the suppressor T cells in LE rats. In LE, we postulated that helper T cells are involved in the induction of AA, and a defect in the suppressor T cell function or numbers would subject LE to the development of AA. SD rats, on the other hand, with higher suppressor T cell numbers, were less susceptible to AA. adjuvant arthritis ; lymphocytic response ; PHA ; Con A ; lymph node

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Inhibition by 6-Mercaptopurine of Polyarthritis induced by Freund's Adjuvant

Cited by 36 publications

References 13 publications

Evaluation of Intra-Articular Thio-Tepa in Rheumatoid Arthritis

Evaluation of Intra-Articular Thio-Tepa in Rheumatoid Arthritis

Mechanisms Underlying the Suppression of Adjuvant‐Induced Arthritis by 6‐Mercaptopurine

Lymphocyte Subsets and Mitogen Induced Proliferation in Adjuvant Arthritis. Part II. Changes in Function and Numbers of Lymph Nodes T Lymphocytes.

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