Is sudden infant death syndrome (SIDS) an autoimmune disorder of endogenous vasoactive neuropeptides?

Sudden infant death syndrome (SIDS) remains a perplexing diagnosis with conflicting laboratory investigation and lack of a biologically plausible aetiology. Investigations into the endogenous vasoactive neuropeptides, including pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are revealing the critical role these substances have in homeostasis including thermo- and cardiovascular regulation. For example, studies in PACAP receptor-deficient mice have revealed sudden neonatal death attributed to respiratory control defects, possibly due to mutations in genes encoding components of PACAP signalling pathways. PACAP and VIP belong to the secretin/glucagon superfamily of hormones and function as vasoactive neuropeptides. They act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to small peptide fragments. They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions. Vasoactive neuropeptides have a known role in thermoregulation and deficiency states are associated with higher neonatal death rates in rats. PACAP plays a significant role in carbohydrate and lipid metabolism and impairment of functioning has potentially serious consequences. It is postulated PACAP and VIP receptors in brain may become compromised through autoimmune phenomena resulting in cardio-respiratory dysfunction and death. This paper discusses the potential role of certain vasoactive neuropeptides in causing autoimmune responses in susceptible infants predisposing them to SIDS.