Effect of environmental pollutants on the production of pro-inflammatory cytokines by normal human dermal keratinocytes

The effect of the environmental pollutants, diesel exhaust particles (DEP) and formaldehyde (FA), on the production of pro-inflammatory cytokines (int erleukin (IL)-1 alpha, IL-1 beta, tumor necrosis factor (TNF)-alpha and IL- 8) by normal human dermal keratinocytes (hKCs) was investigated. Normal hKC s were incubated with various concentrations of DEP (0.4, 0.8, 4, or 20 mu g/ml) or FA (0.25, 0.5, 1, or 5 mu g/ml), and cytokine production was then determined by enzyme-linked immunosorbent assay (ELISA). DEP (20 mu g/ml) i nduced IL-1 beta production without altering cell growth. The increased pro duction of IL-1 beta induced by this concentration of DEP was further enhan ced by the presence of phorbol 12-myristate 13-acetate (PMA), although PMA alone did not affect the levels of IL-1 beta. IL-8 production was also incr eased by DEP (0.4 and 0.8 mu g/ml), which is consistent with the results th at these concentrations of DEP increased the number of cells significantly after 72 h incubation. Although FA alone did not stimulate the production o f IL-1 beta or IL-8 by keratinocytes, FA (0.5 mu g/ml and 5 mu g/ml) signif icantly increased IL-8 and IL-1 beta production, respectively, in cells sti mulated with PMA. IL-1 alpha production was not modulated by FA or DEP even in the presence of PMA. TNF-alpha was produced by unstimulated keratinocyt es at barely detectable levels after 48 h incubation. Although basal levels of TNF-alpha in the culture supernatants were increased after stimulation with PMA, neither pollutant alone nor combination with PMA affected the lev els of TNF-alpha. These in vitro findings suggest that environmental pollut ants may act as modulating factors of cutaneous inflammation by affecting t he ability of keratinocytes to release pro-inflammatory cytokines. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.