Induction of IL-4 and IL-6 synthesis in vitro: variation in signaling requirements and kinetics are dependent on the anatomic source of the responding mononuclear cells
Secrist, H.; Holers, V.M.; Levine, A.; Egan, M.; Nahm, M.H.; Butch, A.W.; Peters, M.
Regional Immunology 3(6): 341-348
1990
ISSN/ISBN: 0896-0623 PMID: 2132759 Document Number: 349845
We have shown differences in regulation of cytokine mRNA expression in human tonsil, spleen, and peripheral blood. After PHA stimulation of peripheral blood, IL-2, IL-4, and IL-6 mRNA were expressed with similar kinetics: peak expression occurred after four hours and subsequently declined over 48 hr. In PHA-stimulated splenic and tonsillar MNC, IL-2 and IL-6 mRNA were expressed later, with peak expression occurring after eight hours of stimulation and no mRNA detectable after 40 hr of stimulation. The intensity of the IL-6 mRNA signal and the amount of IL-6 secreted was much greater in MNC from peripheral blood than in spleen and tonsil and correlated with the percentage of monocytes in MNC from each tissue. IL-4 mRNA expression differed in all three tissues: PHA-stimulated tonsillar MNC expressed IL-4 mRNA with a major peak at eight hours and a minor peak at 24 hr after stimulation. The kinetics of mRNA were not due to effects of mixed cell populations. The same bimodal peak was observed in purified tonsillar T lymphocytes, and the minor 24-hr peak was dependent on IL-4 mRNA synthesis by cells expressing high amounts of VLA-beta 1 antigen (CDw29) on their surface and which lacked the CD45 epitope recognized by the mAb 2H4. Splenic MNC did not express IL-4 mRNA when stimulated with a number of mitogens and only exhibited IL-4 mRNA expression when stimulated with the combination of PHA and PMA or anti-CD3. Thus, IL-4 mRNA has markedly different kinetics and intensity of expression in spleen, peripheral blood, and tonsil.