The Journal of Immunology, Vol 143, Issue 6 1737-1744, Copyright © 1989 by American Association of Immunologists

ARTICLES

Regulation of murine lymphokine production in vivo. Ultraviolet radiation exposure depresses IL-2 and enhances IL-4 production by T cells through an IL-1-dependent mechanism

BA Araneo, T Dowell, HB Moon and RA Daynes
Department of Pathology, University of Utah Health Science Center, Salt Lake City 84132.

The exposure of experimental animals to the inflammatory effects of ultraviolet radiation (UVR) is known to cause depressions in their ability to initiate and effectuate various types of cellular immune responses. Contact-type and delayed-type hypersensitivity, plus the ability to generate protective forms of anti-viral and anti-tumor immunity, are all affected by the prior exposure of normal animals to the effects of this physical agent. Presently, the cellular and molecular mechanism(s) responsible for mediating the changes in immune function observed in UVR-exposed animals is not fully understood. Herein we report that one reproducible consequence of exposing normal mice to low doses of UVR is a dramatic change in the pattern of lymphokines secreted by their activated T cells. Lymphocytes isolated from UVR-exposed donors produce/secrete greatly reduced levels of the T cell lymphokines IL-2 and IFN-gamma activation in vitro with protein Ag of the polyclonal T cell stimulant anti-CD3. The secretion of IL-4 by these lymphocyte cultures, however, is consistently elevated in comparison to normal controls. Further studies determined that a similar change in lymphokine production was induced when mice were treated with either bacterial LPS or rIL-1 beta, a cytokine known to be elevated in vivo after UVR or LPS exposure. The ability of IL-1 to facilitate a change in the capacity of T lymphocytes to produce/secrete lymphokines after in vitro activation does not appear to represent a direct effect of this cytokine on lymphocyte or accessory cell targets because addition of IL-1 beta to cultures of Ag-primed lymphocytes obtained from normal donors was incapable of altering the pattern of lymphokine production. Collectively, our present results add further support to the hypothesis that UVR-induced elevations in endogenous IL- 1 are, in part, responsible for the immunomodulatory effects of UVR. These findings provide compelling evidence that UVR, plus other agents capable of endogenously stimulating the production of IL-1, may function to alter the expression of different effector mechanisms in vivo. This could be facilitated through selective reductions in lymphokines produced by Th-1-type cells (IL-2 and IFN-gamma) and a simultaneous augmentation in a lymphokine produced by Th-2-type cells (IL-4).

This article has been cited by other articles:

				L. Wang, M. Toda, K. Saito, T. Hori, T. Horii, H. Shiku, K. Kuribayashi, and T. Kato Post-immune UV irradiation induces Tr1-like regulatory T cells that suppress humoral immune responses Int. Immunol., January 1, 2008; 20(1): 57 - 70. [Abstract] [Full Text] [PDF]

				N. M. Khaskhely, M. Maruno, H. Uezato, A. Takamiyagi, S. T. Ramzi, K. M. A. Kasem, K.-i. Kariya, T. Toda, Y. Hashiguchi, E. A. G. Landires, et al. Low-Dose UVB Contributes to Host Resistance against Leishmania amazonensis Infection in Mice through Induction of Gamma Interferon and Tumor Necrosis Factor Alpha Cytokines Clin. Vaccine Immunol., May 1, 2002; 9(3): 677 - 686. [Abstract] [Full Text] [PDF]

				M. B. M. Teunissen, G. Piskin, S. d. Nuzzo, R. M. R. Sylva-Steenland, M. A. de Rie, and J. D. Bos Ultraviolet B Radiation Induces a Transient Appearance of IL-4+ Neutrophils, Which Support the Development of Th2 Responses J. Immunol., April 15, 2002; 168(8): 3732 - 3739. [Abstract] [Full Text] [PDF]

				A. Boonstra, A. van Oudenaren, B. Barendregt, L. An, P. J. M. Leenen, and H. F. J. Savelkoul UVB irradiation modulates systemic immune responses by affecting cytokine production of antigen-presenting cells Int. Immunol., November 1, 2000; 12(11): 1531 - 1538. [Abstract] [Full Text] [PDF]

				J. A. Lekstrom-Himes, R. A. LeBlanc, L. Pesnicak, M. Godleski, and S. E. Straus Gamma Interferon Impedes the Establishment of Herpes Simplex Virus Type 1 Latent Infection but Has No Impact on Its Maintenance or Reactivation in Mice J. Virol., July 15, 2000; 74(14): 6680 - 6683. [Abstract] [Full Text]

				G. O. Simkin, J.-S. Tao, J. G. Levy, and D. W. C. Hunt IL-10 Contributes to the Inhibition of Contact Hypersensitivity in Mice Treated with Photodynamic Therapy J. Immunol., March 1, 2000; 164(5): 2457 - 2462. [Abstract] [Full Text] [PDF]

				L. L. Hill, V. K. Shreedhar, M. L. Kripke, and L. B. Owen-Schaub A Critical Role for Fas Ligand in the Active Suppression of Systemic Immune Responses by Ultraviolet Radiation J. Exp. Med., April 19, 1999; 189(8): 1285 - 1294. [Abstract] [Full Text] [PDF]

				L. A. Herraiz, W.-C. Hsieh, R. S. Parker, J. E. Swanson, A. Bendich, and D. A. Roe Effect of UV Exposure and {beta}-Carotene Supplementation on Delayed-Type Hypersensitivity Response in Healthy Older Men J. Am. Coll. Nutr., December 1, 1998; 17(6): 617 - 624. [Abstract] [Full Text] [PDF]

				V. K. Shreedhar, M. W. Pride, Y. Sun, M. L. Kripke, and F. M. Strickland Origin and Characteristics of Ultraviolet-B Radiation-Induced Suppressor T Lymphocytes J. Immunol., August 1, 1998; 161(3): 1327 - 1335. [Abstract] [Full Text] [PDF]

				V. Shreedhar, T. Giese, V. W. Sung, and S. E. Ullrich A Cytokine Cascade Including Prostaglandin E2, IL-4, and IL-10 Is Responsible for UV-Induced Systemic Immune Suppression J. Immunol., April 15, 1998; 160(8): 3783 - 3789. [Abstract] [Full Text] [PDF]