Regulation of breathing pattern by IL-10

Abstract

Proinflammatory cytokines like interleukin-1β (IL-1β) affect the control of breathing. Our aim is to determine the effect of the anti-inflammatory cytokine IL-10 οn the control of breathing. IL-10 knockout mice (IL-10^-/-, <i>n</i> = 10) and wild-type mice (IL-10^+/+, <i>n</i> = 10) were exposed to the following test gases: hyperoxic hypercapnia 7% CO₂-93% O₂, normoxic hypercapnia 7% CO₂-21% O₂, hypoxic hypercapnia 7% CO₂-10% O₂, and hypoxic normocapnia 3% CO₂-10% O₂. The ventilatory function was assessed using whole body plethysmography. Recombinant mouse IL-10 (rIL-10; 10 μg/kg) was administered intraperitoneally to wild-type mice (<i>n</i> = 10) 30 min before the onset of gas challenge. IL-10 was administered in neonatal medullary slices (10-30 ng/ml, <i>n</i> = 8). We found that IL-10^-/- mice exhibited consistently increased frequency and reduced tidal volume compared with IL-10^+/+ mice during room air breathing and in all test gases (by 23.62 to 33.2%, <i>P</i> < 0.05 and -36.23 to -41.69%, <i>P</i> < 0.05, respectively). In all inspired gases, the minute ventilation of IL-10^-/- mice was lower than IL-10^+/+ (by -15.67 to -22.74%, <i>P</i> < 0.05). The rapid shallow breathing index was higher in IL-10^-/- mice compared with IL-10^+/+ mice in all inspired gases (by 50.25 to 57.5%, <i>P</i> < 0.05). The intraperitoneal injection of rIL-10 caused reduction of the respiratory rate and augmentation of the tidal volume in room air and also in all inspired gases (by -12.22 to -29.53 and 32.18 to 45.11%, <i>P</i> < 0.05, respectively). IL-10 administration in neonatal rat (<i>n</i> = 8) in vitro rhythmically active medullary slice preparations did not affect either rhythmicity or peak amplitude of hypoglossal nerve discharge. In conclusion, IL-10 may induce a slower and deeper pattern of breathing.