Neuronal regulation of interleukin 6 secretion in murine spleen: adrenergic and opioidergic control.
The PNS was anticipated to be involved in the modulation of immune responses. To study aspects of this neuronal-immune communication, a recently developed tissue slice method was used to study the effects of adrenergic and opioidergic transmitters on interleukin 6 (IL-6) secretion in the spleen. The alpha 2-adrenergic agonist p-aminoclonidine (10(-7) M) inhibited IL-6 secretion (control vs. p-aminoclonidine, 100.0 +/- 4.76 vs. 59.3 +/- 6.6% of control values; p < 0.001). The alpha 1-adrenergic agonist methoxamine (10(-8) M) also inhibited IL-6 secretion (100.0 +/- 4.8 vs. 71.5 +/- 3.8%; p < 0.001). The endogenous opioids beta-endorphin (10(-10) M), methionine-enkephalin (10(-9) M), and leucine-enkephalin (10(-9) M) inhibited IL-6 secretion as well (p = 0.0051, p = 0.0337, and p = 0.0226, respectively). Electrical stimulation of spleen slices inhibited IL-6 secretion (100.0 +/- 4.3 vs. 56.7 +/- 4.6% of control values; p < 0.001). The involvement of alpha-adrenergic and opioidergic molecules in this electrically induced inhibition was shown by the use of antagonists. Electrical inhibition of IL-6 secretion was attenuated by phentolamine (10(-7) M; p = 0.0345), by naloxone (10(-6) M; p = 0.0046), by cyprodime (10(-8) M; p = 0.0014), and by the combination of cyprodime (10(-7) M) plus phentolamine (10(-8) M; p < 0.0001). We conclude from the complementary studies that the inhibition of IL-6 secretion induced by electrical pulses was mostly mediated by alpha-adrenergic and mu-opioidergic endogenous transmitters.
Straub
R H
RH
Department of Internal Medicine I, University Medical Center Regensburg, Germany.
Herrmann
M
M
Berkmiller
G
G
Frauenholz
T
T
Lang
B
B
Schölmerich
J
J
Falk
W
W
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009019:Morphinans / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D011957:Receptors, Opioid / Q000819:agonists / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000294:innervation* / Q000378:metabolism; D001615:beta-Endorphin / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000700:Analgesics; D004745:Enkephalins; D015850:Interleukin-6; D009019:Morphinans; D009292:Narcotic Antagonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C058450:cyprodime; D009270:Naloxone; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D001615:beta-Endorphin; C016986:apraclonidine; D011433:Propranolol; D007545:Isoproterenol; D003000:Clonidine; D010646:Phentolamine