Modulation of helper T cell function by prostaglandins.
OBJECTIVE
To determine the influence of prostaglandins on the production of interleukins 2, 4, and 5 (IL-2, IL-4, and IL-5), interferon-gamma (IFN gamma), granulocyte-macrophage colony-stimulating factor, and transformating growth factor beta 1 by CD4+ T cells.


METHODS
TH0, TH1, and TH2 T cell clones were stimulated in the presence and absence of the prostaglandin E1 (PGE1) analog misoprostol and PGE2. Lymphokine production was analyzed by using a semiquantitative polymerase chain reaction with lymphokine-specific primer sets and/or by determining lymphokine activity in bioassays.


RESULTS
PGE2 and misoprostol have distinct effects on different functional T helper cells. TH1 cells, which predominantly produce IL-2 and IFN gamma, are completely inhibited, while TH2 cells, which preferentially produce IL-4 and IL-5, are largely unaffected. Misoprostol and PGE2 are equivalent in their ability to modulate T cell function. In the presence of prostaglandins, TH0-like helper cells, which are characterized by the coproduction of multiple lymphokines, function as TH2 cells; however, they do not differentiate into TH2 T cells.


CONCLUSIONS
Prostaglandins that are produced in inflamed tissue can regulate the functional capabilities of infiltrating T cells. In the presence of PGE2, TH1-like responses are suppressed and TH0-like responses are shifted toward a TH2-like pattern dominated by the production of IL-4 and IL-5. Inhibition of prostaglandin production by antiinflammatory agents might restore TH1 responses with local production of IL-2 and IFN gamma.
Gold
K N
KN
Mayo Clinic, Rochester, Minnesota.
Weyand
C M
CM
Goronzy
J J
JJ
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008222:Lymphokines / Q000187:drug effects / Q000378:metabolism*; D016595:Misoprostol / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011458:Prostaglandins E / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D007376:Interleukin-2; D015848:Interleukin-5; D008222:Lymphokines; D011458:Prostaglandins E; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016595:Misoprostol; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor