In vitro cytokine release from rat type II pneumocytes and alveolar macrophages following exposure to JP-8 jet fuel in co-culture

Abstract

Alveolar type II epithelial cells (AIIE) and pulmonary alveolar macrophages (PAM) are involved in pulmonary toxicity of JP-8 jet fuel exposure. To further elucidate their inflammatory mechanisms, the effect(s) of JP-8 jet fuel on cytokine secretion were examined in a transformed rat AIIE cell line (RLE-6TN) culture alone, primary PAM (from Fischer 344 rats) culture alone, and the co-culture of AIIE and primary PAM. A series of JP-8 jet fuel concentrations (0-0.8 microg/ml), which may actually be encountered in alveolar space of lungs exposed in vivo, were placed in cell culture for 24 h. Cultured AIIE alone secreted spontaneously interleukin (IL)-1beta and -6 [below detectable limits for IL-10 and tumor necrosis factor-alpha (TNF-alpha)], whereas cultured PAM alone secreted IL-1beta, -10, and TNF-alpha, in a concentration-dependent manner. These data suggest that the release of cytokines, not only from PAM but also from AIIE cells, may contribute to JP-8 jet fuel-induced inflammatory response in the alveolar space. However, the co-cultures of AIIE and PAM showed no significant changes in IL-1beta, -6, and TNF-alpha at any JP-8 jet fuel concentration compared to control values. These cytokine levels in co-cultures of AIIE and PAM were inversely related to these of cultured AIIE or PAM alone. Interestingly, IL-10 levels in the co-culture system were concentration-dependently increased up to 1058% at JP-8 concentrations of 0.8 microg/ml, although under detectable limits in cultured AIIE alone and no significant concentration change in cultured PAM alone. It appears that PAM may possibly act via paracrine and/or autocrine pathways to signal AIIE cells to regulate cytokine release.