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Effett of melatonin on T helper cell activity
Pharmacological Research, Vol. 22. Supplement 3,1990
53
EFFETT OF MELATONIN ON T HELPER CELL ACTIVITY M.C. Caroleo (1), D. Frasca (2). C. Mancini (2). G. Nistico (1) and G. Doria (2) (1) Institute of Pharmacology, Faculty of Medicine, Catanzaro and (2) Laboratory of Pathology ENEA C.R.E., ceseccte, Rome Key words: melatonin - cyclophosphamide - agin - Th activity We examined the effect of Melatonin (MEL), the main hormone of the pineal gland, on the generation of T helper (Th) cells in young mice and in mice immunodepressed by aging or cyclophosphamide (Cy) treatment. At the age of 2 and 12 months male (C57BLll OxDBAl2)F1 mice were left untreated or treated for 4 days by daily subcutaneous injections of MEL (10 mg/kg). Immediately before the injection of MEL, mice were carriedprimed by l.v. injection of horse red blood cells (HRBC) to induce Th cells. Th cell activity of pooled spleen cells (4 mice/group) from HRBC-primed mice, untreated or treated with MEL, was tritrated 4 days later by adding graded numbers of carried-primed cells to cultures containg a constant number of normal spleen cells from unprimed mice and the nepten-cemer conjugate 2,4,6-trinitrophenyl (TNP)-HRBC. The anti-TNP antibody response given by 1x 10' spleen cells from HRBC-primed mice cultured 5 with 2xl0 TNP-HRBC was also assayed. The anti-TNP response, as direct PFC/culture, was evetueted et doy 4 end 5 of culture. As evetueted from the in lo'itroanti TNP antibody response, carried primed spleen cells exhibit no significant change in Th cell activity when derived from MELtreated as compared to untreated young mice. In contrast MEL administration to mice immunodepressed by 8ging or Cy treatment was able to ehance to a great extent the impaired helper activity displayed by their spleen cells. Moreover MEL was able to significl:lOtly enhance the anti-TNP PCF response extbtten by the whole spleen cell population from young, old or Cy -treeted mice. Taken together the data show that MEL displ8YS major effects under immunodepressive conditions. Moreover, the finding that MEL is able to increase the in lo'itroanti-TNP PCF response of the whole spleen in young, old and Cy-treated mice is compatible with the possibility that the neurohormone acts not only on activated T cells, but also on B or accessory cells. Experiment in progress are addressed to identify the cellular target of MEL and to clarify the role of MEL on the immune response 1) Brown GM, Niles LP. Studies on melatonin and other pineal factors. In: Martin JB, Reichilin S, eds. Clinical neuroendocrinology. New Vork: Accademic Press, 1982,253-285. 2) Doria G, D'Agostaro G, serevim M. Age-dependent changes ob B-cell reactiYtty and T cell-T cell interaction in the in vitro antibody response. Cell. Immunol., 1980,53: 195-206
I043-6618/90/22II10053--o I/$03.00/0
© 1990 The Italian Pharmacological Society
53
EFFETT OF MELATONIN ON T HELPER CELL ACTIVITY M.C. Caroleo (1), D. Frasca (2). C. Mancini (2). G. Nistico (1) and G. Doria (2) (1) Institute of Pharmacology, Faculty of Medicine, Catanzaro and (2) Laboratory of Pathology ENEA C.R.E., ceseccte, Rome Key words: melatonin - cyclophosphamide - agin - Th activity We examined the effect of Melatonin (MEL), the main hormone of the pineal gland, on the generation of T helper (Th) cells in young mice and in mice immunodepressed by aging or cyclophosphamide (Cy) treatment. At the age of 2 and 12 months male (C57BLll OxDBAl2)F1 mice were left untreated or treated for 4 days by daily subcutaneous injections of MEL (10 mg/kg). Immediately before the injection of MEL, mice were carriedprimed by l.v. injection of horse red blood cells (HRBC) to induce Th cells. Th cell activity of pooled spleen cells (4 mice/group) from HRBC-primed mice, untreated or treated with MEL, was tritrated 4 days later by adding graded numbers of carried-primed cells to cultures containg a constant number of normal spleen cells from unprimed mice and the nepten-cemer conjugate 2,4,6-trinitrophenyl (TNP)-HRBC. The anti-TNP antibody response given by 1x 10' spleen cells from HRBC-primed mice cultured 5 with 2xl0 TNP-HRBC was also assayed. The anti-TNP response, as direct PFC/culture, was evetueted et doy 4 end 5 of culture. As evetueted from the in lo'itroanti TNP antibody response, carried primed spleen cells exhibit no significant change in Th cell activity when derived from MELtreated as compared to untreated young mice. In contrast MEL administration to mice immunodepressed by 8ging or Cy treatment was able to ehance to a great extent the impaired helper activity displayed by their spleen cells. Moreover MEL was able to significl:lOtly enhance the anti-TNP PCF response extbtten by the whole spleen cell population from young, old or Cy -treeted mice. Taken together the data show that MEL displ8YS major effects under immunodepressive conditions. Moreover, the finding that MEL is able to increase the in lo'itroanti-TNP PCF response of the whole spleen in young, old and Cy-treated mice is compatible with the possibility that the neurohormone acts not only on activated T cells, but also on B or accessory cells. Experiment in progress are addressed to identify the cellular target of MEL and to clarify the role of MEL on the immune response 1) Brown GM, Niles LP. Studies on melatonin and other pineal factors. In: Martin JB, Reichilin S, eds. Clinical neuroendocrinology. New Vork: Accademic Press, 1982,253-285. 2) Doria G, D'Agostaro G, serevim M. Age-dependent changes ob B-cell reactiYtty and T cell-T cell interaction in the in vitro antibody response. Cell. Immunol., 1980,53: 195-206
I043-6618/90/22II10053--o I/$03.00/0
© 1990 The Italian Pharmacological Society