concanavalin-a and pristane

Systemic lupus erythematosus (SLE) is characterized by inflammatory and dysregulatory immune responses including overactive B cells, overproduction of proinflammatory cytokines, and T cell hyperactivity. PGE(2) modulates a variety of immune processes at sites of inflammation, including production of inflammatory cytokines. However, the role of PGE(2) in dysregulatory inflammatory and immune responses in lupus remains unclear. We investigated whether PGE(2) mediates production of inflammatory cytokines in pristane-induced lupus BALB/c mice. Our results showed that levels of serum and BAL PGE(2) and LPS-stimulated production of PGE(2) by peritoneal macrophages were remarkably increased in pristane-induced lupus mice compared to healthy controls. Exogenous PGE(2) enhanced production of IL-6, IL-10, and NO but decreased TNF-alpha by macrophages and augmented IFN-gamma, IL-6, and IL-10 by splenocytes from pristane-induced lupus mice compared to healthy controls. Exogenous PGE(2) also enhanced production of IFN-gamma, IL-6, and IL-10 by thymocytes from pristane-induced lupus mice. Indomethacin (Indo), a PGE(2) synthesis inhibitor, greatly inhibited LPS-induced production of IL-6 and IL-10 by macrophages from pristane-induced lupus mice, while enhanced TNF-alpha. Indo remarkably inhibited Con A-increased production of IFN-gamma, IL-6, and IL-10 by splenocytes and thymocytes from pristane-induced lupus mice. Therefore, our findings suggest that endogenous PGE(2) may mediate dysregulation of production of proinflammatory cytokines, such as IL-6, IL-10, and IFN-gamma, and NO in pristane-induced lupus mice.

Topics: Animals; Bronchoalveolar Lavage Fluid; Cells, Cultured; Concanavalin A; Cyclooxygenase Inhibitors; Cytokines; Dinoprostone; Disease Models, Animal; Female; Indomethacin; Inflammation Mediators; Interferon-gamma; Interleukin-10; Interleukin-6; Lipopolysaccharides; Lupus Erythematosus, Systemic; Lymphocytes; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; Nitric Oxide; Spleen; Terpenes; Thymus Gland; Time Factors; Tumor Necrosis Factor-alpha; Up-Regulation

The present study showed a novel finding that the development of adjuvant-induced arthritis (AA) in Lewis rats was completely prevented by incomplete Freund's adjuvant (IFA) injected 21 or 28 days before complete Freund's adjuvant (CFA) challenge. Hexadecane also completely prevented AA and squalane, methyl oleate and pristane moderately prevented AA, though pristane by itself induced mild arthritis in two out of five rats. Concanavalin A-stimulated lymph node cells (LNCs) isolated from AA rats were able to adoptively transfer the severe polyarthritis to all the naive recipients or even to the IFA pretreated recipients with earlier onset and more rapid progression than those of AA. The LNCs from the donors who had been pretreated with IFA and subsequently challenged with CFA could induce mild arthritis in only two out of eight naive recipients, whereas all the recipients who were challenged with CFA immediately after intravenous injection of these LNCs developed significantly less severe arthritis. However, the LNCs from IFA-pretreated donors failed to prevent AA. According to the T helper type 1 (Th1)/Th2 paradigm, it was suggested that the adjuvant-active vehicles such as IFA, hexadecane, squalane, methyl oleate and pristane, can affect and deviate the Th1/Th2 balance of immune responses in host. CFA could promote the propagation of Th2 cells rather than Th1 cells in these vehicle-pretreated rats through as yet undetermined mechanisms, eventually resulting in the prevention of AA. Finally, we discussed a regulatory role of adjuvant vehicles for induction and suppression of AA.

Topics: Adoptive Transfer; Alkanes; Animals; Arthritis, Experimental; Concanavalin A; Female; Freund's Adjuvant; Lymphocytes; Oleic Acids; Pharmaceutical Vehicles; Rats; Rats, Inbred Lew; Squalene; Terpenes; Th1 Cells; Th2 Cells

Pristane-induced arthritis was investigated in DBA/1, DBA/2, and BALB/c mice, and F1 hybrid mice generated from inter-crosses between these strains. The incidence of disease in F1 hybrid mice was significantly lower than the susceptible parental strains (DBA/1 and BALB/c), and resistance to arthritis was observed in both DBA/2 mice and the (DBA/2 x BALB/c) F1 hybrid mice. Several cellular immune abnormalities were observed in pristane-injected DBA/1 mice. Con A mitogen responses were depressed following pristane injection, and a functional suppressor cell population was detected. Delayed type hypersensitivity responses to type II collagen were observed in pristane injected mice. The intraperitoneal injection of pristane appears to alter immune regulation and induce autoimmune responses to connective tissue components.

Topics: Animals; Arthritis; Carcinogens; Collagen; Concanavalin A; Disease Models, Animal; Hybridization, Genetic; Hypersensitivity, Delayed; Immune Tolerance; Lipopolysaccharides; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Terpenes