Cyclophosphamide Adjuvant Arthritis in Trypanosoma cruzi Infected Rats with Inflammatory Cytokine Effects

GRISELDA DIDOLI, MARIA LUISA BAY, FLAVIA RONDELLI, ADRIANA DEL REY, HUGO BESEDOVSKY, and OSCAR BOTTASSO

ABSTRACT.

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. (J Rheumatol 2003;30:497-504)

Key Indexing Terms:

ADJUVANT ARTHRITIS
TRYPANOSOMA CRUZI
CYCLOPHOSPHAMIDE
CYTOKINES

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From the Instituto de Inmunología, Facultad de Ciencias Médicas de la Universidad Nacional de Rosario, Rosario, Argentina; and the Institute für Normale und Pathologische Physiologie, Marburg, Germany.

Supported by the Secretariat for Science and Technology, National University of Rosario.

G. Didoli, MD; M.L. Bay, PhD; F. Rondelli, MD; O. Bottasso, MD, PhD, Instituto de Inmunología, Facultad de Ciencias Médicas de la Universidad Nacional de Rosario; A. Del Rey, PhD; H. Besedovsky, MD, PhD, Institute für Normale und Pathologische Physiologie.

Address reprint requests to Dr. O. Bottasso, Instituto de Inmunologia, Facultad de Ciencias Medicas, Santa Fe 3100, Rosario (2000), Argentina.

Submitted January 16, 2000; revision accepted August 30, 2002.

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