A study published in the journal of Clinical Immunology demonstrates that the cytokine profiles in generalized anxiety disorder (GAD) individuals show traits of Th1 and Th2 deficiencies but are associated with a predominant Th17 phenotype, particularly in the presence of substance P (SP).
Substance P has been shown to stimulate the inflammatory response, contributing to control of infections primarily by enhancing Th1 pathways. In addition, psychological stress leads to increases in SP, and chronically stressed individuals are more vulnerable to infections.
In the journal of Clinical Immunology study, Barros and colleagues drew peripheral blood from unmedicated patients with anxiety and healthy subjects, and measured T cell proliferation and cytokine profiles after polyclonal activation of peripheral blood mononuclear cells cultures with phytohemagglutinin, and following in vitro SP and glucocorticoid (GC) challenges.
Cultures from anxious individuals demonstrated lower T cell proliferation in response to SP as compared to controls, attributable to both lower cell viability and low IL-2 levels, while GC decreased proliferation in controls and had no effect in anxious subjects. In activated cultures from anxious subjects, the production of Th1 cytokines was not altered by SP addition, while this neuropeptide up-regulated the release of IFN-γ in polyclonally activated T cell cultures from healthy subjects.
On the other hand, activated cell cultures from anxious individuals produced higher amounts of IL-17 and TNF-α, which increased even further after SP addition, but were unchanged when GC was added, compared to decreases in IL-17 upon GC stimulation in healthy subjects. Also, levels of the anti-inflammatory cytokine IL-10 decreased upon GC stimulation in healthy subjects but were unchanged in the anxious ones.
According to the authors, a deficient Th1 pathway in chronically stressed individuals could explain their increased susceptibility to infections.
As Th17 hyperactivity has been extensively linked to the pathogenesis of inflammatory conditions such as systemic lupus erythematosus, multiple sclerosis, and chronic inflammatory bowel disease, excessive Th17 activation in the context of GC insensitivity could hold clues to the association of stress and autoimmune disease exacerbations.