Impact of interleukin-1 and interleukin-6 in murine primary schistosomiasis.

BACKGROUND

Immunization with schistosome antigens invariably elicits a plethora of cytokines and, hence, it is reasonable to assume that these cytokines influence host responses to challenge lung-stage larvae and, consequently, the adult worm burden, and may be responsible for the erratic data generally observed in protection studies against schistosome infection.

METHODS

Schistosoma mansoni-infected mice were administered with recombinant interleukin (IL)-1beta or IL-6 to evaluate the impact of cytokines in host responses to lung-stage schistosomula, and subsequent effects on adult worm parameters. Plasma lipid levels were assayed by colorimetric enzymatic tests and antibody responses by ELISA. Cytokine profile in peripheral blood mononuclear cells was evaluated by RT-PCR.

RESULTS

S. mansoni infection elicited, at the time of parasite residency in the lung, significant increase in free fatty acids (FA) and decrease in cholesterol plasma levels in C57BL/6 and CD1 mice, and stimulation of mRNA expression for cytokines of T helper type (Th) 2 in BALB/c, Th1 in C57BL/6, and Th1/Th2 in CD1 mice. However, no specific antibody production was evident in any mouse strain. In BALB/c mice, exogenous IL-1beta-related plasma free FA level significant increase, stimulation of expression of IL-1 and IL-12 mRNA, and considerable increase in percent of specific antibody-producing mice were associated with significant reduction in adult worm burden and egg load. In contrast, exogenous IL-1beta elicited decrease in free FA plasma levels, and down-regulation of cytokines' mRNA expression in C57BL/6 and CD1 mice, changes associated with aggravation of the worm burden. Likewise, exogenous IL-6 failed to stimulate increase in plasma free FA levels or percent of antibody-producing mice except in BALB/c mice, effects that were protective for the host in BALB/c and for the parasite in C57BL/6 and CD1 mice.

CONCLUSION

These findings were discussed in relation to the erratic data of protection experiments with schistosome subunit antigens in different mouse strains.