Cyclophosphamide adjuvant arthritis in Trypanosoma cruzi infected rats with inflammatory cytokine effects

• Published in: Journal of rheumatology 2003-03, Vol.30 (3), p.497-504
• Main Authors: DIDOLI, Griselda, BAY, Maria Luisa, RONDELLI, Flavia, DEL REY, Adriana, BESEDOVSKY, Hugo, BOTTASSO, Oscar
• Format: Article
• Language: English
• Subjects: Animals; Antigens - pharmacology; Antirheumatic Agents; Arthritis, Experimental - chemically induced; Arthritis, Experimental - immunology; Arthritis, Experimental - parasitology; Biological and medical sciences; Cell Division - drug effects; Cell Division - immunology; Chagas Disease - complications; Chagas Disease - immunology; Chronic Disease; Cyclophosphamide; Diseases of the osteoarticular system; Inflammatory joint diseases; Interleukin-10 - metabolism; Interleukin-12 - metabolism; Interleukin-2 - metabolism; Lymph Nodes - cytology; Lymphocytes - immunology; Lymphocytes - metabolism; Male; Medical sciences; Mitogens - pharmacology; Rats; Rats, Inbred Strains; Trypanosoma cruzi - immunology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0315-162X; 1499-2752

OBJECTIVE: To analyze whether the cyclophosphamide (CYC) induced reestablishment of adjuvant arthritis (AA) in chronically Trypanosoma cruzi infected rats correlates with changes in the secretion of pro- and antiinflammatory cytokines by popliteal lymph node cells. METHODS: Inbred "l" rats infected with T. cruzi 90 days earlier and age matched controls were given CYC (25 mg/kg body weight) or physiologic saline 48 h before arthritis induction. Popliteal lymph node cells were collected at the time of AA induction (48 h after CYC treatment) or during the peak response, to study the concanavalin-A (ConA) or Mycobacterium tuberculosis-driven in vitro proliferation of several cytokines in their culture supernatants. Results. Infected rats given CYC were recovered from the otherwise decreased ConA induced proliferation seen at the time of peak AA. The CYC mediated reestablishment of AA in T. cruzi infected rats coexisted with an increased presence of tumor necrosis factor-a in supernatants from either antigen or ConA stimulated cultures as well as interleukin 12 (IL-12) in the latter case. CYC also lowered to normal the increased IL-10 levels from ConA stimulated cultures that the T. cruzi group displayed at the time of inducing AA. Conclusion. The process by which CYC restores the clinical expression of AA affects the balance between cytokines that influence the regulation of arthritis in favor of the inflammatory component.