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Am J Physiol Regul Integr Comp Physiol 275: R1185-R1191, 1998;
0363-6119/98 $5.00
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Vol. 275, Issue 4, R1185-R1191, October 1998

Interleukin-4 inhibits spontaneous sleep in rabbits

Tetsuya Kushikata1, Jidong Fang1, Ying Wang2, and James M. Krueger1

1 Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Washington 99164; and 2 Department of Physiology, The University of Tennessee, Memphis, Tennessee 38163

Proinflammatory cytokines, including interleukin-1beta (IL-1beta ) and tumor necrosis factor-alpha , are involved in sleep regulation. IL-4 is an antiinflammatory cytokine that inhibits proinflammatory cytokine production. The hypothesis that IL-4 should attenuate sleep was studied by determining the effects of IL-4 on rabbit spontaneous sleep. Thirty-six rabbits were used. Four doses of IL-4 (0.25, 2.5, 25, and 250 ng) were injected intracerebroventricularly during the rest (light) period. One dose of IL-4 (25 ng) was injected during the active (dark) cycle. Appropriate time-matched control injections of saline were done in the same rabbits on different days. The three highest doses of IL-4 significantly inhibited spontaneous non-rapid eye movement sleep if IL-4 was given during the light cycle. The highest dose of IL-4 (250 ng) also significantly decreased rapid eye movement sleep. On the other hand, IL-4 administered at dark onset had no effect on sleep. The sleep inhibitory properties of IL-4 provide additional evidence for the hypothesis that a brain cytokine network is involved in the regulation of physiological sleep.

non-rapid eye movement sleep; rapid eye movement sleep; electroencephalogram; cytokines; brain temperature


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