Gulf War Syndrome (GWS) remains a contentious diagnosis with conflicting laboratory investigation and lack of a biologically plausible aetiology. This paper discusses the potential role of
maxadilan, a potent sandfly vasoactive
peptide, in causing autoimmune responses in susceptible individuals through possible molecular mimicry with
pituitary adenylate cyclase activating polypeptide (
PACAP) and the PAC1R receptor.
Gulf War Syndrome may share some causative pathology with
Chronic Fatigue Syndrome (CFS), a disorder characterised by prolonged
fatigue and
debility mostly associated with post-
infection sequelae although ongoing
infection is unproven. Immunological aberration associated with an expanding group of vasoactive
neuropeptides in the context of molecular mimicry and inappropriate immunological memory has been recently raised as possible cause of CFS. Vasoactive
neuropeptides 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.
Maxadilan, while not sharing substantial sequence homology with
PACAP is a known agonist of the
PACAP specific receptor (PAC1R) and therefore emulates these functions. Moreover a specific amino acid sequence
peptide deletion within
maxadilan converts it to a
PACAP receptor antagonist raising the possibility of this substance provoking a CFS like response in humans exposed to it. This paper describes a biologically plausible mechanism for the development of a GWS-like chronic
fatigue state based on loss of immunological tolerance to the vasoactive
neuropeptide PACAP or its receptor following
bites of the sandfly Phlebotomus papatasi and injection of the
vasodilator peptide maxadilan. Exacerbation of this autoimmune response as a consequence of recent or simultaneous multiple vaccination exposures deserves further investigation. While the possible association between the relatively recently discovered vasoactive
neuropeptides and chronic
fatigue conditions has only recently been reported in the literature, this paper explores links for further research into GWS and CFS.