Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1991 Apr;84(1):175–180. doi: 10.1111/j.1365-2249.1991.tb08144.x

Effects of in vivo hyperthermia on natural killer cell activity, in vitro proliferative responses and blood mononuclear cell subpopulations.

M Kappel 1, C Stadeager 1, N Tvede 1, H Galbo 1, B K Pedersen 1
PMCID: PMC1535372  PMID: 2015709

Abstract

This work was designed to test the hypothesis that elevations in body temperature of humans induce immunostimulation. Eight healthy volunteers were immersed in a water bath (water temperature 39.5 degrees C) for 2 h, during which their rectal temperature rose to 39.5 degrees C. On a later day they served as their own controls, being immersed into thermoneutral water (34.5 degrees C) for 2 h. Blood samples were collected before immersion, at body temperatures of 38 degree C, 39 degree C and 39.5 degree C, and 2 h after water immersion. The interleukin-2 (IL-2) enhanced natural killer (NK) cell activity (lysis per fixed number of mononuclear cells), as well as the proportion and total number of NK cells (CD16+ cells), increased significantly during hyperthermia compared with control values. The lymphocyte proliferative responses did not differ significantly between hyperthermia and thermoneutral conditions. The proportion of pan-T (CD3+) cells was maximally depressed 2 h after water immersion. The decreased proportion of CD3+ cells was mainly due to a decreased percentage of CD4+ cells (not significant). The proportion of B cells (CD19+ cells) did not fluctuate significantly, while a marked and significant increase in monocyte proportion (CD14+ cells) was found 2 h after hyperthermia. Two hours after hot water immersion the lymphocyte concentration declined while the neutrophil and monocyte concentrations were augmented. Induced hyperthermia causes significantly increased serum cortisol, plasma norepinephrine and plasma epinephrine concentrations compared to controls. It is possible that the altered immune functions induced by elevated body temperature can be ascribed to altered composition and function of blood mononuclear cells induced by elevated levels of stress hormones.

Full text

PDF
175

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BENNETT I. L., Jr, NICASTRI A. Fever as a mechanism of resistance. Bacteriol Rev. 1960 Mar;24(1):16–34. doi: 10.1128/br.24.1.16-34.1960. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ben-Jonathan N., Porter J. C. A sensitive radioenzymatic assay for dopamine, norepinephrine, and epinephrine in plasma and tissue. Endocrinology. 1976 Jun;98(6):1497–1507. doi: 10.1210/endo-98-6-1497. [DOI] [PubMed] [Google Scholar]
  3. Bernheim H. A., Kluger M. J. Fever: effect of drug-induced antipyresis on survival. Science. 1976 Jul 16;193(4249):237–239. doi: 10.1126/science.935867. [DOI] [PubMed] [Google Scholar]
  4. Carmichael L. E., Barnes F. D., Percy D. H. Temperature as a factor in resistance of young puppies to canine herpesvirus. J Infect Dis. 1969 Dec;120(6):669–678. doi: 10.1093/infdis/120.6.669. [DOI] [PubMed] [Google Scholar]
  5. Cohen P., Warren S. L. A STUDY OF THE LEUKOCYTOSIS PRODUCED IN MAN BY ARTIFICIAL FEVER. J Clin Invest. 1935 Jul;14(4):423–433. doi: 10.1172/JCI100693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dash R. J., England B. G., Midgley A. R., Jr, Niswender G. D. A specific, non-chromatographic radioimmunoassay for human plasma cortisol. Steroids. 1975 Nov;26(5):647–661. doi: 10.1016/0039-128x(75)90057-4. [DOI] [PubMed] [Google Scholar]
  7. Downing J. F., Martinez-Valdez H., Elizondo R. S., Walker E. B., Taylor M. W. Hyperthermia in humans enhances interferon-gamma synthesis and alters the peripheral lymphocyte population. J Interferon Res. 1988 Apr;8(2):143–150. doi: 10.1089/jir.1988.8.143. [DOI] [PubMed] [Google Scholar]
  8. Downing J. F., Taylor M. W. The effect of in vivo hyperthermia on selected lymphokines in man. Lymphokine Res. 1987 Spring;6(2):103–109. [PubMed] [Google Scholar]
  9. Herberman R. B. Natural killer (NK) cells and their possible roles in resistance against disease. Clin Immunol Rev. 1981;1(1):1–65. [PubMed] [Google Scholar]
  10. Hoffman T., Hirata F., Bougnoux P., Fraser B. A., Goldfarb R. H., Herberman R. B., Axelrod J. Phospholipid methylation and phospholipase A2 activation in cytotoxicity by human natural killer cells. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3839–3843. doi: 10.1073/pnas.78.6.3839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Katz P., Zaytoun A. M., Lee J. H., Jr The effects of in vivo hydrocortisone on lymphocyte-mediated cytotoxicity. Arthritis Rheum. 1984 Jan;27(1):72–78. doi: 10.1002/art.1780270112. [DOI] [PubMed] [Google Scholar]
  12. Onsrud M., Thorsby E. Influence of in vivo hydrocortisone on some human blood lymphocyte subpopulations. I. Effect on natural killer cell activity. Scand J Immunol. 1981;13(6):573–579. doi: 10.1111/j.1365-3083.1981.tb00171.x. [DOI] [PubMed] [Google Scholar]
  13. Ortaldo J. R., Mantovani A., Hobbs D., Rubinstein M., Pestka S., Herberman R. B. Effects of several species of human leukocyte interferon on cytotoxic activity of NK cells and monocytes. Int J Cancer. 1983 Mar 15;31(3):285–289. doi: 10.1002/ijc.2910310306. [DOI] [PubMed] [Google Scholar]
  14. Parrillo J. E., Fauci A. S. Comparison of the effector cells in human spontaneous cellular cytotoxicity and antibody-dependent cellular cytotoxicity: differential sensitivity of effector cells to in vivo and in vitro corticosteroids. Scand J Immunol. 1978;8(2):99–107. doi: 10.1111/j.1365-3083.1978.tb00501.x. [DOI] [PubMed] [Google Scholar]
  15. Pedersen B. K., Beyer J. M. Characterization of the in vitro effects of glucocorticosteroids on NK cell activity. Allergy. 1986 Apr;41(3):220–224. doi: 10.1111/j.1398-9995.1986.tb00303.x. [DOI] [PubMed] [Google Scholar]
  16. Pedersen B. K., Beyer J. M., Rasmussen A., Klarlund K., Pedersen B. N., Helin P. Methylprednisolone pulse therapy induced fall in natural killer cell activity in rheumatoid arthritis. Acta Pathol Microbiol Immunol Scand C. 1984 Oct;92(5):319–323. doi: 10.1111/j.1699-0463.1984.tb00094.x. [DOI] [PubMed] [Google Scholar]
  17. Pedersen B. K., Kharazmi A. Inhibition of human natural killer cell activity by Pseudomonas aeruginosa alkaline protease and elastase. Infect Immun. 1987 Apr;55(4):986–989. doi: 10.1128/iai.55.4.986-989.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pedersen B. K. Natural killer cells in relation to disease and treatment. Allergy. 1985 Nov;40(8):547–557. doi: 10.1111/j.1398-9995.1985.tb00881.x. [DOI] [PubMed] [Google Scholar]
  19. Pedersen B. K., Tvede N., Hansen F. R., Andersen V., Bendix T., Bendixen G., Bendtzen K., Galbo H., Haahr P. M., Klarlund K. Modulation of natural killer cell activity in peripheral blood by physical exercise. Scand J Immunol. 1988 Jun;27(6):673–678. doi: 10.1111/j.1365-3083.1988.tb02400.x. [DOI] [PubMed] [Google Scholar]
  20. Roberts N. J., Jr, Sandberg K. Hyperthermia and human leukocyte function. II. Enhanced production of and response to leukocyte migration inhibition factor (LIF). J Immunol. 1979 May;122(5):1990–1993. [PubMed] [Google Scholar]
  21. Shen R. N., Hornback N. B., Shidnia H., Lu L., Broxmeyer H. E., Brahmi Z. Effect of whole-body hyperthermia and cyclophosphamide on natural killer cell activity in murine erythroleukemia. Cancer Res. 1988 Aug 15;48(16):4561–4563. [PubMed] [Google Scholar]
  22. Shen R. N., Hornback N. B., Shidnia H., Shupe R. E., Brahmi Z. Whole-body hyperthermia decreases lung metastases in lung tumor-bearing mice, possibly via a mechanism involving natural killer cells. J Clin Immunol. 1987 May;7(3):246–253. doi: 10.1007/BF00915730. [DOI] [PubMed] [Google Scholar]
  23. Tvede N., Pedersen B. K., Hansen F. R., Bendix T., Christensen L. D., Galbo H., Halkjaer-Kristensen J. Effect of physical exercise on blood mononuclear cell subpopulations and in vitro proliferative responses. Scand J Immunol. 1989 Mar;29(3):383–389. doi: 10.1111/j.1365-3083.1989.tb01137.x. [DOI] [PubMed] [Google Scholar]
  24. Tønnesen E., Christensen N. J., Brinkløv M. M. Natural killer cell activity during cortisol and adrenaline infusion in healthy volunteers. Eur J Clin Invest. 1987 Dec;17(6):497–503. doi: 10.1111/j.1365-2362.1987.tb01148.x. [DOI] [PubMed] [Google Scholar]
  25. Zänker K. S., Lange J. Whole body hyperthermia and natural killer cell activity. Lancet. 1982 May 8;1(8280):1079–1080. doi: 10.1016/s0140-6736(82)92142-0. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES