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Neuropeptide regulation of interleukin-1 activities

Capacity of α-melanocyte stimulating hormone to inhibit interleukin-1-inducible responses in vivo and in vitro exhibits target cell selectivity

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Abstract

α-Melanocyte stimulating hormone (α-MSH), a 13 amino acid neuropeptide produced by the pituitary gland, was found to markedly inhibit the capacity of exogenously administered interleukin-1 (IL-1) to stimulate the enhanced synthesis of acute-phase proteins and induce neutrophilia in vivo. The administration of ACTH or glucocorticosteroids lacked most of these direct IL-1 inhibitory properties. Therefore, in addition to the previously reported antipyretic action of α-MSH, this hormone can also inhibit two other known IL-1-sensitive cellular targets in vivo. Further, α-MSH was incapable of modifying the comitogenic influence of IL-1 on murine thymocytes or on an IL-1 responsive T-cell line. These findings suggest a target cell specificity to the IL-1 inhibitory activities of α-MSH and fail to support the hypothesis that α-MSH functions through competitive inhibition of specific cellular receptors for IL-1.

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References

  1. Luger, T. A., B. M. Stadler, B. M. Luger, B. J. Mathieson, M. Mage, J. A. Schmidt, andJ. J. Oppenheim. 1981. Murine epidermal cell-derived thymocyte-activating factor resembles murine interleukin-1.J. Immunol. 128:2147–2152.

    Google Scholar 

  2. Powanda, M. C., andW. R. Beisel. 1982. Hypothesis: Leukocyte endogenous mediator/ endogenous pyrogen/lymphocyte activating factor modulates the development of nonspecific and specific immunity.Am. J. Clin. Nutr. 35:762–768.

    Google Scholar 

  3. Gery, I. 1984. Interleukin-1: Uniqueness of its production and spectrum of activities.Lymphokines 9:109–125.

    Google Scholar 

  4. Sipe, J. D., S. D. Vogel, M. B. Sztein, M. Skinner, andA. S. Cohen. 1982. The role of interleukin-1 in acute phase serum amyloid A (SAA) and serum amyloid P (SAP) biosynthesis.In C-Reactive Protein and the Plasma Protein Response to Tissue Injury. I. Kushner, J. E. Volanakis, and H. Gewurz, editors. New York Academy of Sciences, New York. 137–148.

    Google Scholar 

  5. Gahring, L. C., M. Baltz, andM. B. Pepys. 1984. The effect of ultraviolet radiation on the production of ETAF/IL-1 in vivo and in vitro.Proc. Natl. Acad. Sci. U.S.A. 81:1198–1202.

    Google Scholar 

  6. Kurt-Jones, E. A., D. I. Beller, S. B. Mizel, andE. R. Unanue. 1985. Identification of a membrane associated interleukin-1 in macrophages.Proc. Natl. Acad. Sci. U.S.A. 82:1204–1208.

    Google Scholar 

  7. Gahring, L. C., andR. A. Daynes. 1986. Desensitization to the inflammatory effects of ultraviolet radiation is mediated through mechanisms which are distinct from those responsible for endotoxin tolerance.J. Immunol. 136:2868.

    Google Scholar 

  8. Snyder, D. S., andE. R. Unanue. 1982. Corticosteroids inhibit murine macrophage Ia expression and interleukin-1 production.J. Immunol. 129:1803–1805.

    Google Scholar 

  9. Wood, D. D., andD. Hammerman. 1985. Presence and role of interleukin-1 in human arthritis.Prog. Leuk. Biol. 2:63–71.

    Google Scholar 

  10. Dower, S. K., S. R. Kronheim, C. J. March, P. J. Conlon, T. P. Hopp, S. Gillis, andD. L. Urdal. 1985. Detection and characterization of high affinity plasma membrane receptors for human interleukin-1.J. Exp. Med. 162:501–515.

    Google Scholar 

  11. Arend, W. P., F. G. Joslin, andR. J. Massoni. 1985. Effects of immune complexes on production by human monocytes of interleukin-1 or an interleukin-1 inhibitor.J. Immunol. 134:3868–3875.

    Google Scholar 

  12. Roberts, N. J., A. H. Prill, andR. N. Mann. 1985. Interleukin-1 and inhibitor production by human macrophages exposed to influenza virus or respiratory syncytial virus.Prog. Leuk. Biol. 2:409–418.

    Google Scholar 

  13. Liao, Z., A. Haimovitz, Y. Chen, andD. L. Rosenstreich. 1985. Characterization of a human interleukin-1 inhibitor.J. Immunol. 134:3882–3886.

    Google Scholar 

  14. Liao, Z., R. A. Grimshaw, andD. L. Rosenstreich. 1984. Identification of a specific interleukin-1 inhibitor in the urine of febrile patients.J. Exp. Med. 159:126–136.

    Google Scholar 

  15. Rosenstreich, D. L., J. Korn, S. Kabir, andK. M. Brown. 1985. Studies on a urine derived human interleukin-1 inhibitor.Prog. Leuk. Biol. 2:419–428.

    Google Scholar 

  16. Murphy, M. T., andJ. M. Lipton. 1982. Peripheral administration of α-MSH reduces fever in older and younger rabbits.Peptides 3:775–779.

    Google Scholar 

  17. Lipton, J. M., J. R. Glyn, andJ. A. Zimmer. 1981. ACTH and α-melanotropin in central temperature control.Fed. Proc. 4:2760–2764.

    Google Scholar 

  18. Clark, W. G., M. Holdeman, andJ. M. Lipton. 1985. Analysis of the antipyretic action of α-MSH in rabbits.J. Physiol. 359:459–465.

    Google Scholar 

  19. Lipton, J. M. 1985. Antagonism of IL-1 fever by the neuropeptide α-MSH.In The Physiologic, Metabolic, and Immunologic Actions of IL-1. (M. J. Kluger, J. J. Oppenheim, and M. C. Powanda, editors.) Alan R. Liss, New York. 121–132.

    Google Scholar 

  20. Glyn-Ballinoer, J. R., G. L. Bunardini, andJ. M. Lipton. 1983. α-MSH injected into the septal region reduces fever in rabbits.Peptides 4:199–203.

    Google Scholar 

  21. Holdeman, M., andJ. M. Lipton. 1985. Effects of massive doses of α-MSH on thermoregulation in the rabbit.Brain Res. Bull. 14:327–330.

    Google Scholar 

  22. Murphy, M. T., D. B. Richards, andJ. M. Lipton. 1983. Antipyretic potency of centrally administered α-melanocyte stimulating hormone.Science 221:192–193.

    Google Scholar 

  23. Glyn, J. R., andJ. M. Lipton. 1981. Hypothermic and antipyretic effects of centrally administered ACTH (1-24) and α-melanotropin.Peptides 2:177–187.

    Google Scholar 

  24. Kandasamy, S. B., andB. A. Williams. 1984. Hypothermic and antipyretic effects of ACTH (1-24) and α-melanotropin in guinea pigs.Neuropharmacology 23:49–53.

    Google Scholar 

  25. Kampschmidt, R. F., andH. F. Upchurch. 1977. Possible involvement of leukocyte endogenous mediator in granulopoiesis.Proc. Soc. Exp. Biol. Med. 155:89–93.

    Google Scholar 

  26. Smith, R. J., S. C. Speziale, andB. J. Bowman. 1985. Properties of interleukin-1 as a complete secretagogue for human neutrophils.Biochem. Biophys. Res. Commun. 130:1233–1240.

    Google Scholar 

  27. Gahring, L. C., A. Buckley, andR. A. Daynes. 1985. The presence of epidermal derived thymocyte activating factor/interleukin-1 in normal human stratum corneum.J. Clin. Invest. 76:1585–1591.

    Google Scholar 

  28. Kaye, J., J. Porcelli, B. Tite, B. Jones, andC. A. Janeway. 1983. Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen presenting cells in the activation of T cells.J. Exp. Med. 158:836.

    Google Scholar 

  29. Kaye, J., andC. A. Janeway. 1984. The FAB fragment of a directly activating monoclonal antibody that precipitates a disulfide-linked heterodimer from a helper T-cell clone blocks activating by either allogeneic Ia or antigen and self Ia.J. Exp. Med. 159:1397.

    Google Scholar 

  30. Kastin, A. J., C. Nissen, K. Nikolics, K. Medzihradszky, D. H. Coy, I. Teplan, andA. V. Schally. 1976. Distribution of [3H]α-MSH in rat brain.Brain Res. Bull. 1:19–26.

    Google Scholar 

  31. Blalock, J. E., D. Harbour-McMenamin, andE. M. Smith. 1985. Peptide hormones shared by the neuroendocrine and immunologic systems.J. Immunol. 135:858s-861s.

    Google Scholar 

  32. Dinarello, C. A., andS. M. Wolf. 1982. Molecular basis of fever in humans.Am. J. Med. 72:799–819.

    Google Scholar 

  33. Sipe, J. D. 1985. Interleukin-1 and regulation of acute phase protein synthesis.Lymphokines 12:87–106.

    Google Scholar 

  34. Dinarello, C. A. 1984. Induction of acute phase reactants by interleukin-1.Adv. Inflamm. Res. 8:203–225.

    Google Scholar 

  35. Baracos, V. H., H. P. Rodemann, C. A. Dinarello, andA. L. Goldberg. 1983. Stimulation of muscle protein degradation and prostaglandin E release by leukocytic pyrogen (IL-1). A mechanism for the increased degradation of muscle proteins during fever.N. Engl. J. Med. 308:553–558.

    Google Scholar 

  36. Schmidt,J. A., S. B. Mizel, D. Cohen, andI. Green. 1982. Interleukin-1, a potential regulator of fibroblast proliferation.J. Immunol. 128:2177–2182.

    Google Scholar 

  37. Mizel, S. B., J. M. Dayer, S. M. Krane, andS. E. Merghenhagen. 1981. Stimulation of rheumatoid synovial cell collagenase and prostaglandin production by partially purified lymphocyte-activating factor (IL-1).Proc. Natl. Acad. Sci. U.S.A. 78:2474–2477.

    Google Scholar 

  38. Dayer, J. M., S. M. Krane, G. G. Russell, andD. R. Robinson. 1976. Production of collagenase and prostaglandins by isolated adherent rheumatoid synovial cells.Proc. Natl. Acad. Sci. U.S.A. 73:945–949.

    Google Scholar 

  39. Woloski, B. M R. N. J., E. M. Smith, W. J. Meyer III, G. M. Fuller, andJ. E. Blalock. 1985. Corticotropin-releasing activity of monokines.Science 230:1035–1037.

    Google Scholar 

  40. Simon, P. L., J. B. Willoughby, andW. F. Willoughby. 1983. Inhibition of T-cell activation by alpha-1-antiprotease is reversed by purified rabbit interleukin-1.In Interleukins, Lymphokines, and Cytokines. J. J. Oppenheim, and S. Cohen, editors. Academic Press, New York. 487–492.

    Google Scholar 

  41. Dinarello, C. A., L. J. Rosenwasser, andS. M. Wolff. 1981. Demonstration of a circulating suppressor factor of thymocyte proliferation during endotoxin fever in humans.J. Immunol. 127:2517–2519.

    Google Scholar 

  42. Holdeman, M., O. Khorram, W. K. Samson, andJ. M. Lipton. 1984. Fever specific changes in central MSH and CRF concentrations.Am. J. Physiol. 248:R125-R129.

    Google Scholar 

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Robertson, B.A., Gahring, L.C. & Daynes, R.A. Neuropeptide regulation of interleukin-1 activities. Inflammation 10, 371–385 (1986). https://doi.org/10.1007/BF00915821

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