Exogenous interleukin-12 (IL-12) exacerbates Cryptosporidium parvum infection in gamma interferon knockout mice

Experimental infection of BALB/c- or C57BL/6-gamma-interferon-knockout (GKO ) mice with Cryptosporidium parvum results in infection in both strains wit h different outcomes of disease. The BALB/c-GKO mice recover from infection , whereas the C57BL/6-GKO mice succumb to infection in less than 2 weeks. D ifferences in cytokine mRNA expression suggested that recovery may involve other cytokines. To determine whether the addition of either a Th1 or Th2 c ytokine could alter the outcome of infection, we treated GKO mice with eith er recombinant (r)IL-4 or rIL-12 1 day before infection (DBI) or daily. No effect on the oocyst shedding patterns in either strain nor an increase in survival of the C57BL/6-GKO mice was observed in the rIL-4-treated mice. Wh ereas one dose of 0.5 mug rIL-12 given 1 DBI had no effect on oocyst sheddi ng, we found that daily doses of rIL-12 administered intraperitoneally exac erbated C. parvum infection in both animal models. Administration of rIL-12 shortened the survival time in the C57BL/6-GKO mice and prevented BALB/c-G KO mice from recovering from infection. Specific proliferation of T cells t o cryptosporidial antigen and Th1 and Th2 mRNA cytokine expression was mark edly decreased in rIL-12-treated mice. Nitric oxide (NO) may have played a minor role in the decreased proliferation observed since levels of NO prese nt in the splenocyte cultures from rIL-12-treated mice in response to paras ite antigen stimulation were higher than those observed in controls. Thus, we propose that resistance to and recovery from C. parvum infections involv es a fine balance in the amount and timing of Th1 and Th2 cytokines. (C) 20 01 Academic Press.