Apnea associated with infection and inflammation is a major medical concern in preterm infants. Prostaglandin E 2 (PGE 2) serves as a critical mediator between infection and apnea. We hypothesize that alteration of the microsomal PGE synthase-1 (mPGES-1) PGE 2 pathway influences respiratory control and response to hypoxia.
Nine-d-old wild-type (WT) mice, mPGES-1 heterozygote (mPGES-1 +/–), and mPGES-1 knockout (mPGES-1 –/–) mice were used. Respiration was investigated in mice using flow plethysmography after the mice received either interleukin-1β (IL-1β) (10 µg/kg) or saline. Mice were subjected to a period of normoxia, subsequent exposure to hyperoxia, and finally either moderate (5 min) or severe hypoxia (until 1 min after last gasp).
IL-1β worsened survival in WT mice but not in mice with reduced or no mPGES-1. Reduced expression of mPGES-1 prolonged gasping duration and increased the number of gasps during hypoxia. Response to intracerebroventricular PGE 2 was not dependent on mPGES-1 expression.
Activation of mPGES-1 is involved in the rapid and vital response to severe hypoxia as well as inflammation. Attenuation of mPGES-1 appears to have no detrimental effects, yet prolongs autoresuscitation efforts and improves survival. Consequently, inhibition of the mPGES-1 pathway may serve as a potential therapeutic target for the treatment of apnea and respiratory disorders.