Cytokine and eicosanoid regulation by Schistosoma mansoniduring LSE penetration.

Cercarial penetration, in low to moderate numbers, does not cause a normal skin inflammatory response; therefore, the authors sought to determine whether cercariae can down-regulate keratinocyte activation and thus the secretion of pro-inflammatory cytokines and eicosanoids. Human living skin equivalent (LSE, Organogenesis) consisting of dermal, epidermal and stratum corneum-like layers was used as the skin substrate. The surface of the LSE membrane was exposed to 100 ng IFNgamma or ~850 cercariae for 18 h. Incubation media and tissue was then assayed for IL-1alpha, IL-6, IL-8, TNFalpha, 5-HETE, 12-HETE, PGF(2), LTB(4), and LTC(4) via RIA and Western Blots. TNFalpha was not detected. Secreted IL-1alpha levels were (mean +/- S.E.M. (n)): Control, 1.03 ng +/- 0.15 (11); IFNgamma 1.90 ng +/- 0.48 (5); cercariae, 1.79 ng +/- 0.22 (22). In spite of this increase, cercariae down-regulated IL-8 (cercariae 11.13 +/- 1.70 ng vs. IFNgamma = 16.47 +/- 0.29 ng, p = 0.04) and LTB(4) (cercariae = 98.86 +/- 19.65 pg/0.1 ml vs. IFNgamma = 193.42 +/- 44.21 pg/0.1 ml p = 0.02). No changes were seen in IL-6, 12-HETE, 5-HETE, and PGE(2) levels. It is concluded that cercarial penetration causes a release of IL-1alpha consistent with skin trauma; however, schistosomulae may regulate the production of chemotactic (neutrophils, macrophages, T-cells, etc.) and activation factors such as IL-8 and LTB(4).