Methanol induces a discrete transcriptional dysregulation that leads to cytokine overproduction in activated lymphocytes.
Methanol is an important cause of acute alcohol intoxication; it is ubiquitously present at home and in the workplace. Although the existing literature provides a reasonable insight into the immunological impact of ethanol and to a much lesser extent of isopropanol, much less data are available on methanol. We hypothesized on structural grounds that methanol would share the immunosuppressive properties of the two other short-chain alcohols. We report here that methanol increases the proliferative capacity of human T lymphocytes and synergizes with the activating stimuli to augment cytokine production. The cytokine upregulation was observed in vitro at methanol concentrations as low as 0.08% (25mM) as measured by interleukin-2, interferon-γ, and tumor necrosis factor-α release in T cells. Methanol did not affect the antigen receptor-mediated early signaling but promoted a selective and differential activation of the nuclear factor of activated T cells family of transcription factors. These results were further substantiated in a mouse model of acute methanol intoxication in which there was an augmented release of proinflammatory cytokines in the serum in response to the staphylococcal enterotoxin B. Our results suggest that methanol has a discrete immunological footprint of broad significance given the exposure of the general population to this multipurpose solvent.
Désy
Olivier
O
Laval University Cancer Research Center, Quebec City, Quebec, Canada G1R 2J6.
Carignan
Damien
D
Caruso
Manuel
M
de Campos-Lima
Pedro O
PO
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D004768:Enterotoxins / Q000494:pharmacology; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D000432:Methanol / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D012997:Solvents / Q000633:toxicity*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects* / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects* / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; D004768:Enterotoxins; D012997:Solvents; C031818:enterotoxin B, staphylococcal; D000432:Methanol