Interleukin‐1 Interaction with neuroregulatory systems: Selective enhancement by recombinant human and mouse interleukin‐1 of in vitro opioid peptide receptor binding in rat brain

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Abstract
Interleukin‐1 (IL‐1) exerts a wide variety of biological effects on various cell types and may be regarded as a pleiotropic peptide hormone. Biological evidence suggests that IL‐1 participates in the modulation of central nervous system physiology and behaviour in a fashion characteristic of neuroendocrine hormones. In this investigation, recombinant (r) human (h) IL‐1 and r mouse (m) IL‐1 were examined for their modulation of opioid peptide receptor binding in vitro. Experiments were performed on frozen sections of rat brain. Receptor binding of radiolabeled substance P and of radiolabeled neurotensin were not significantly affected by the presence of rIL‐1s. Recombinant IL‐1s, however, significantly enhanced specific binding of 125I‐beta‐endorphin (125I‐beta‐END) and of D‐ala2‐(tyrosyl‐3,5‐3H)enkephalin‐(5‐D‐leucine) (3H‐D‐ALA), equipotently and in a concentration‐dependent manner with maximal activity occurring at a concentration of 10 LAF units/ml. The increased binding of 125I‐β‐END and 3H‐D‐ALA was blocked steroselectively by (−)‐naloxone and by etorphine, suggesting detection of opiate receptors. In addition, brain distribution patterns of receptors labeled in the presence of rIL‐1s corresponded to patterns previously published for opiate receptors. Autoradiographic visualization of receptors revealed that rIL‐1s in the different areas of the brain exert their effect on opioid binding with comparable potencies. The data suggest that certain central nervous system effects of IL‐1s may be mediated by their selective interaction with opiatergic systems at the receptor level.