The Role of Th1/Th2 Cytokine Balance in Gulf War-Related Illness

The aetiology of Gulf-War (GW) related illnesses remains unclear. The proposal has been made that multiple vaccines, given under the stress of deployment with additional effects of the T helper 2 (Th2) adjuvant pertussis could skew the immune response towards a Th2 profile. The Th2 profile, characterised by the cytokines intefleukin-4 (IL-4) and IL-lO, has been associated with syndromes such as allergic disease, hypersensitivity and depression, symptoms characteristic of which are often reported by sick GW veterans (GWVs). We are studying whether self-reported illness in GWVs is associated with a Th2 shift by examining Th2 (IL-4, IL-i 0) and Th1 (IL-2, interferon-gamma) intracellular cytokine staining in CD4 and CD8 T lymphocytes by flow cytometry after mitogenic stimulation. To date we have recruited GWVs with and without illness, as well as a group of control servicemen with similar symptoms who were either not deployed (era controls) or deployed to the Bosnia conflict and healthy laboratory control subjects (LCs). We find changes in cytokine profiles in each of the 3 service groups compared with the LCs. Our data suggest that deployment to the Gulf and multi-symptom illness are associated with immune activation, with different patterns seen in sick and well veterans of the Gulf conflict. We await the full acquisition of clinical and vaccine record data, to determine the clinical correlates of our immunological findings.