Drug actions on delayed-type hypersensitivity in rats with developing and established adjuvant arthritis

Hambleton, P; McMahon, Stephen B.

doi:10.1007/bf01966465

Cited by 24 publications

(11 citation statements)

References 22 publications

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“…Although effective in this assay, leflunomide, surprisingly, did not seem to demonstrate immunosuppressive activity, at least in failing to inhibit the ex-vivo response of lymphocytes to mitogens in healthy rats [4]. These results were independently confirmed by Pasternak et al [24] and Hambleton and McMahon [16]. Pasternak found further that leflunomide significantly reduced edema, fibrinogen levels and erythrocyte sedimentation rates, whereas both leflunomide and cyclosporin A (CsA) could reduce the delayed-type hypersensitivity (DTH) response to mycobacterial antigens on day 9 followed by a rebound to an enhanced DTH response on day 21.…”

Section: Adjuvant Arthritissupporting

confidence: 76%

Effects of leflunomide on immune responses and models of inflammation

Bartlett¹,

Anagnostopulos²,

Zielinski

et al. 1993

Springer Semin Immunopathol

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Section: Adjuvant Arthritissupporting

confidence: 76%

Effects of leflunomide on immune responses and models of inflammation

Bartlett¹,

Anagnostopulos²,

Zielinski

et al. 1993

Springer Semin Immunopathol

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“…Further, although effective in this assay, to our surprise, leflunomide did not demonstrate immunosuppressive activity, at least concerning the ex-vivo response of lymphocytes to mitogens in healthy rats [2]. These results were independently confirmed by Pasternak et al [6], as well as Hambleton and McMahon [8]. Pasternak found further that leflunomide significantly reduced edema, fibrinogen levels, and erythrocyte sedimentation rates.…”

Section: Leflunomide Inhibits the Adjuvant Disease Of Ratssupporting

confidence: 67%

Leflunomide (HWA 486), a novel immunomodulating compound for the treatment of autoimmune disorders and reactions leading to transplantation rejection

Bartlett¹,

Dimitrijevic²,

et al. 1991

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Leflunomide has been shown to be very effective in preventing and curing several autoimmune animal diseases. Further, this agent is as effective as cyclosporin A in preventing the rejection of skin and kidney transplants in rats. Preliminary results from patients suffering from severe cases of rheumatoid arthritis demonstrated that clinical and immunological parameters could be improved with leflunomide therapy. Mode of action studies revealed that this substance antagonizes the proliferation inducing activity of several cytokines and is cytostatic for certain cell types. In this light, we could show that tyrosine phosphorylation of the RR-SRC peptide substrate and the autophosphorylation of the epidermal growth factor (EGF) receptor were, dose dependently, inhibited by leflunomide. EGF activates the intrinsic tyrosine kinase of its receptor, which stimulates the phosphorylation of a variety of peptides, the amino acid residue in all cases is tyrosine. These results indicate that much of leflunomide's activity could be due to the inhibition of tyrosine-kinase(s), which is an important general mechanism for the proliferation of various cell types. Thus, leflunomide, which is effective against autoimmune diseases and reactions leading to graft rejection, would seem to have a mode of action separating it from known immunosuppressive drugs.

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“…DTH reaction is a form of cellular immune reaction mediated by T DTH cells. 46) Hambleton and McMahon 3) have reported the induction of a dermal DTH response to a mycobacterial antigen that decreased in magnitude with the development of adjuvant arthritis. But other studies are in conflict to this report in adjuvant arthritis.…”

Section: Discussionmentioning

confidence: 99%