JP-8 jet fuel exposure induces inflammatory cytokines in rat skin.
The Department of Defense (DoD) has identified that one of the main complaints of personnel exposed to JP-8 jet fuel is irritant dermatitis. The purpose of this investigation is to describe the JP-8-induced inflammatory cytokine response in skin. JP-8 jet fuel or acetone control (300 microl) was applied to the denuded skin of rats once a day for 7 days. Skin samples from the exposed area were collected 2 and 24 h after the final exposure. Histological examination of skin biopsies showed neutrophilic inflammatory infiltrate. Reverse transcription-polymerase chain reaction (RT-PCR) was performed utilizing skin total RNA to examine the expression of various inflammatory cytokines. The CXC chemokine GROalpha was significantly upregulated at both time points, whereas GRObeta was only increased 2 h post final exposure. The CC chemokines MCP-1, Mip-1alpha, and eotaxin were induced at both time points, whereas Mip-1beta was induced only 24 h post exposure. Interleukins-1beta and -6 (IL-1beta and IL-6) mRNAs were significantly induced at both time points, while TNFalpha was not significantly different from control. Enzyme-linked immunosorbent assay (ELISA) of skin protein confirmed that MCP-1, TNFalpha, and IL-1beta were modulated as indicated by PCR analysis. However, skin IL-6 protein content was not increased 2 h post exposure, whereas it was significantly upregulated by jet fuel after 24 h. Data from the present study indicate that repeated (7 days) JP-8 exposure induces numerous proinflammatory cytokines in skin. The increased expression of these cytokines and chemokines may lead to increased inflammatory infiltrate in exposed skin, resulting in JP-8-induced irritant dermatitis.
Gallucci
Randle M
RM
Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, P.O. Box 26901, Oklahoma City, OK 73190, USA. randy-gallucci@ouhsc.edu
O'Dell
Sijy K
SK
Rabe
Daniel
D
Fechter
Laurence D
LD
D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D017931:DNA Primers; D003877:Dermatitis, Contact / Q000378:metabolism / Q000473:pathology; D006838:Hydrocarbons / Q000633:toxicity*; D007249:Inflammation / Q000378:metabolism*; D007375:Interleukin-1 / Q000096:biosynthesis; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020318:Rats, Long-Evans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects
D018925:Chemokines; D019743:Chemokines, CXC; D016207:Cytokines; D017931:DNA Primers; D006838:Hydrocarbons; D007375:Interleukin-1; C098607:JP8 aviation fuel; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha