Role of interleukin 6 (IL-6) in protection from lethal irradiation and in endocrine responses to IL-1 and tumor necrosis factor.
Primary responsibility for the induction of various acute phase reactions has been ascribed to interleukin 1 (IL-1), tumor necrosis factor (TNF), or IL-6, suggesting that these cytokines may have many overlapping activities. Thus, it is difficult to identify the cytokine primarily responsible for a particular biologic effect, since IL-1 and TNF stimulate one another, and both IL-1 and TNF stimulate IL-6. In this work, the contribution of IL-6 in radioprotection, induction of adrenocorticotropic hormone (ACTH), and induction of hypoglycemia was assessed by blocking IL-6 activity. Administration of anti-IL-6 antibody to otherwise untreated mice greatly enhanced the incidence of radiation-induced mortality, indicating that like IL-1 and TNF, IL-6 also contributes to innate resistance to radiation. Anti-IL-6 antibody given to IL-1-treated or TNF-treated mice reduced survival from lethal irradiation, demonstrating that IL-6 is also an important mediator of both IL-1- and TNF-induced hemopoietic recovery. A similar IL-1/IL-6 interaction was observed in the case of ACTH induction. Anti-IL-6 antibody blocked the IL-1-induced increase in plasma ACTH, whereas recombinant IL-6 by itself did not induce such an increase. Anti-IL-6 antibody also mitigated TNF-induced hypoglycemia, but did not reverse IL-1-induced hypoglycemia. It is, therefore, likely that TNF and IL-1 differ in their mode of induction of hypoglycemia. Our results suggest that an interaction of IL-6 with IL-1 and TNF is a prerequisite for protection from radiation lethality, and its interaction with IL-1 for induction of ACTH.
Neta
R
R
Department of Experimental Hematology, Armed Forces Radiobiology Research Institute, Bethesda, Maryland.
Perlstein
R
R
Vogel
S N
SN
Ledney
G D
GD
Abrams
J
J
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D005260:Female; D007003:Hypoglycemia / Q000209:etiology / Q000276:immunology*; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000502:physiology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D011832:Radiation Injuries / Q000276:immunology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*
D007375:Interleukin-1; D015850:Interleukin-6; D011837:Radiation-Protective Agents; D014409:Tumor Necrosis Factor-alpha; D000324:Adrenocorticotropic Hormone