Inhibition of human lymphocyte function by organic solvents.
We studied the direct effect of reactive hydroxyl precursors and inhibitors on CD4+ T-cell function. We used hydrogen peroxide plus ferrous chloride as the hydroxyl radical-generating system and di-methyl sulphourea, di-methyl sulfoxide, pyrrolidine dithiocarbonate, methanol, and ethanol, at a noncytotoxic concentration, as inhibitors. The immune parameter studies were proliferation and interleukin-2 production by peripheral blood lymphocytes stimulated with anti-CD3 antibody, phytohemagglutinin and alloantigens; proliferation, interleukin-2 production and mRNA expression of interleukin-4 and interferon gamma by allogeneic CD4+ T-cell clones stimulated with alloantigens. The results show that lymphocytes produce significant amounts of reactive oxygen species as measured by malondialdehyde produced in cultures. The hydroxyl radical-generating system did not change any of the cellular responses studied although it doubled Malondialdehyde production. Hydroxyl radical scavengers significantly inhibited all responses at doses that didn't significantly decrease malondialdehyde production. DNA analysis failed to show evidence for apoptosis.


CONCLUSIONS
Hydroxyl radical scavengers inhibit lymphocyte mitogenesis by a process that is independent of scavenging hydroxyl radicals.
Shoker
A S
AS
Department of Medicine, University of Saskatchewan, Saskatoon, Canada.
Murabit
M A
MA
Georges
F F
FF
Qualtiere
L F
LF
Deneer
H G
HG
Prasad
K
K
D000640:Amitrole / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003545:Cysteine / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism*; D008715:Methionine / Q000494:pharmacology; D016853:Muromonab-CD3 / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012997:Solvents / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D000975:Antioxidants; D016166:Free Radical Scavengers; D007376:Interleukin-2; D016853:Muromonab-CD3; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D012997:Solvents; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D008315:Malondialdehyde; C038983:1,3-dimethylthiourea; D004247:DNA; D008715:Methionine; D013890:Thiourea; D003545:Cysteine; D004121:Dimethyl Sulfoxide; D000640:Amitrole