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Cytokine-mediated stress responses in the hypothalamus
S63
ACTIVATION KANNAN
OF SYMPATHETIC
l, YOSHIAKI
OUTFLOW
BY INTERLEUKIN
HAYASHIDA2.HIROAKI.
YAMASHITA1.m’phvsiolopv 2Sm@v. . . . -oka Yaha@&rku. Krtakvushu 807. Jaggg Theeffects of interleukin ls(ILlg)
18 IN CONSCIOUS
TADASHI
RATS.
HIROSW
NAKAMURA’,
Universitv of m
Health. l-
on the autonomic nervous system, which may play a critical role in the interactions
between the central nervous system and the immune system, are still controversial. The present study was conducted to examine the effects of IL-ll3 on sympathetic nervous system in conscious rats. Either intravenous (iv.) or intracerebroventricular (i.c.v.) administration of LIB elicited ao increase in renal sympathetic nerve activity(RSNA) accompanied by increases in blood pressure, heart rate and body temperature. Small non-bursting component in RSNA increased, while large bursting component was attenuated. The responses were completely abolished when the animals were pre-treated with the cycloxygenase inhibitor indomethacin, or the ganglionic blocker hexamethonium. Intravenous injection of IL-IS significantly increased plasma catecholamine and ACTH concentration. The results suggest that ILlB produces activation of sympathetic outflow and ACTH release, which may be closely related in the organism’s adaptive response to stress. This work was entrusted to UOEH, using the special Coordination Funds for Promoting Science and Technology.
CARDIOVASCULAR RESPONSE INDUCED IN FREE-MOVING RATS BY INTRA-HYPOTHALAMIC INJECTION OF INTERLEUKIN-16. AK10 MORIMOTO, KEIKO MORIMOTO, AND NAOTOSHI MURAKAMI. Department of Physiology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755, Japan. We investigated the effect of intraperitoneal (i.p.1 injections of interleukin-1B (IL-16) on cardiovascular responses in free-moving rats, using a biotelemetry system. The i.p. injection of a small dose of IL-1B (1 ug/kg) induced a monophasic increase in the blood pressure and heart rate, and that of a large dose (10 ug/kg) induced biphasic increases. Pretreatment with i.p. injection of indomethacin (10 mg/kg), an inhibitor of cyclooxygenase, significantly suppressed the enhancement of the cardiovascular responses and the increase in the plasma norepinephrine (NE) concentration after i-p. injection of IL-1B. Microinjection of IL-16 (1 ng and 10 ng) into the preoptic and anterior hypothalamic (PO/AH) region induced dose-dependent increases in the blood pressure and heart rate in rats. These responses were also suppressed by pretreatment with i.p. indomethacin. In addition, microinjection of prostaglandin E 2 (20 ng and 100 ng) into the PO/AH region increased the blood pressure and heart rate, but that of prostaglandin D2 (100 ng) had no effect. The present results suggest that IL-16 stimulates the release of prostaglandins of the E series, which act on the hypothalamus to induce an activation of sympathetic nervous system. Subsequently the blood pressure, heart rate and the plasma level of NE increase.
CYTOKINE-MEDIATED STRESS RESPONSES IN THE HypoTHALAMuS.
JUNICHlFUKATA.AND
HIROO IMUF&
SecondDivision, Danartmentof Medicine, Kyotn University Facultyof Medicine. 54 ShonoinKawaharacho. Sak~o ku. Kyoto 606, Jaoan. It is well known that exposure to stress has profound effects on several neuroendocrine functions, including increased secretion of adrenocorticotropin (ACTH) and decreased release of luteinizing hormone (LH). Infection, trauma, endotoxemia, and physical exercise, which induce these stress-related
changes, are now known to induce
a cytokine, isolated originally as a lymphocyte activating factor and now termed as interleukin (II&l, in a number of tissues. Since recombinant IL1 has been reported to mimic a lot of stress-induced changes, including those in the nervousand endocrine system,weexaminedwhetherIll inducedendogenously by lipcpolysaccharide (LPS) participated in these hormone responses. LPS administered iv or icv increased plasma ACTH and decreased plasma LH levels. Both anti-IL1 a antiserum and IL-1 receptor antagonist abolished at least the early phases of these hormone responses. ILlmRNA in the hypothalamus, where the cytokine is supposed to act to initiate these hormonal changes, also increased neuroendocrine responses
under these circumstances. These under certain stressful conditions.
data
suggest
that
IL-l
mediates
hypothalamic
ACTIVATION KANNAN
OF SYMPATHETIC
l, YOSHIAKI
OUTFLOW
BY INTERLEUKIN
HAYASHIDA2.HIROAKI.
YAMASHITA1.m’phvsiolopv 2Sm@v. . . . -oka Yaha@&rku. Krtakvushu 807. Jaggg Theeffects of interleukin ls(ILlg)
18 IN CONSCIOUS
TADASHI
RATS.
HIROSW
NAKAMURA’,
Universitv of m
Health. l-
on the autonomic nervous system, which may play a critical role in the interactions
between the central nervous system and the immune system, are still controversial. The present study was conducted to examine the effects of IL-ll3 on sympathetic nervous system in conscious rats. Either intravenous (iv.) or intracerebroventricular (i.c.v.) administration of LIB elicited ao increase in renal sympathetic nerve activity(RSNA) accompanied by increases in blood pressure, heart rate and body temperature. Small non-bursting component in RSNA increased, while large bursting component was attenuated. The responses were completely abolished when the animals were pre-treated with the cycloxygenase inhibitor indomethacin, or the ganglionic blocker hexamethonium. Intravenous injection of IL-IS significantly increased plasma catecholamine and ACTH concentration. The results suggest that ILlB produces activation of sympathetic outflow and ACTH release, which may be closely related in the organism’s adaptive response to stress. This work was entrusted to UOEH, using the special Coordination Funds for Promoting Science and Technology.
CARDIOVASCULAR RESPONSE INDUCED IN FREE-MOVING RATS BY INTRA-HYPOTHALAMIC INJECTION OF INTERLEUKIN-16. AK10 MORIMOTO, KEIKO MORIMOTO, AND NAOTOSHI MURAKAMI. Department of Physiology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755, Japan. We investigated the effect of intraperitoneal (i.p.1 injections of interleukin-1B (IL-16) on cardiovascular responses in free-moving rats, using a biotelemetry system. The i.p. injection of a small dose of IL-1B (1 ug/kg) induced a monophasic increase in the blood pressure and heart rate, and that of a large dose (10 ug/kg) induced biphasic increases. Pretreatment with i.p. injection of indomethacin (10 mg/kg), an inhibitor of cyclooxygenase, significantly suppressed the enhancement of the cardiovascular responses and the increase in the plasma norepinephrine (NE) concentration after i-p. injection of IL-1B. Microinjection of IL-16 (1 ng and 10 ng) into the preoptic and anterior hypothalamic (PO/AH) region induced dose-dependent increases in the blood pressure and heart rate in rats. These responses were also suppressed by pretreatment with i.p. indomethacin. In addition, microinjection of prostaglandin E 2 (20 ng and 100 ng) into the PO/AH region increased the blood pressure and heart rate, but that of prostaglandin D2 (100 ng) had no effect. The present results suggest that IL-16 stimulates the release of prostaglandins of the E series, which act on the hypothalamus to induce an activation of sympathetic nervous system. Subsequently the blood pressure, heart rate and the plasma level of NE increase.
CYTOKINE-MEDIATED STRESS RESPONSES IN THE HypoTHALAMuS.
JUNICHlFUKATA.AND
HIROO IMUF&
SecondDivision, Danartmentof Medicine, Kyotn University Facultyof Medicine. 54 ShonoinKawaharacho. Sak~o ku. Kyoto 606, Jaoan. It is well known that exposure to stress has profound effects on several neuroendocrine functions, including increased secretion of adrenocorticotropin (ACTH) and decreased release of luteinizing hormone (LH). Infection, trauma, endotoxemia, and physical exercise, which induce these stress-related
changes, are now known to induce
a cytokine, isolated originally as a lymphocyte activating factor and now termed as interleukin (II&l, in a number of tissues. Since recombinant IL1 has been reported to mimic a lot of stress-induced changes, including those in the nervousand endocrine system,weexaminedwhetherIll inducedendogenously by lipcpolysaccharide (LPS) participated in these hormone responses. LPS administered iv or icv increased plasma ACTH and decreased plasma LH levels. Both anti-IL1 a antiserum and IL-1 receptor antagonist abolished at least the early phases of these hormone responses. ILlmRNA in the hypothalamus, where the cytokine is supposed to act to initiate these hormonal changes, also increased neuroendocrine responses
under these circumstances. These under certain stressful conditions.
data
suggest
that
IL-l
mediates
hypothalamic