Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis, health, and well-being. Like the stress response, the inflammatory reaction is crucial for survival and is meant to be tailored to the stimulus and time. A full-fledged systemic inflammatory reaction results in stimulation of four major programs: the acute-phase reaction, the sickness syndrome, the pain program, and the stress response, mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Common human diseases such as atopy/allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro- versus anti-inflammatory and T helper (Th)1versus Th2 cytokine balance. Recent evidence also indicates the involvement of pro-inflammatory cytokines in the pathogenesis of atherosclerosis and major depression, and conditions such as visceral-type obesity, metabolic syndrome and sleep disturbances. During inflammation, the activation of the stress system, through induction of a Th2 shift, protects the organism from systemic ‘overshooting’ with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-α and C-reactive protein production and through activation of the corticotropin-releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the ‘systemic anti-inflammatory feedback’ and/or ‘hyperactivity’ of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health. These hypotheses require further investigation, but the answers should provide critical insights into mechanisms underlying a variety of common human immune-related diseases.

Summary Backgound In coeliac disease, following the introduction of a gluten‐free diet, monitoring mucosal disease activity requires repeated small intestinal biopsies. If a test measuring a circulating inflammatory marker was available, this would be clinically valuable. Aim To determine if levels of soluble CD163, a scavenger receptor shed by tissue macrophages, correlated with the inflammatory lesion in coeliac disease. Methods Serum samples were collected from 131 patients with untreated coeliac disease, 40 patients with treated coeliac disease, 92 non‐coeliac disease control subjects and 131 healthy controls. A capture enzyme linked immunosorbance assay was established to measure levels of soluble CD163 in sera. The extent of the histological lesion in coeliac biopsies was assessed using a Marsh grading system. Results Levels of CD163 in untreated coeliac subjects were significantly elevated when compared with the treated coeliac patients, the disease control group and the healthy control subjects (P < 0.0001 in each instance). Moreover, coeliac patients with the most marked histological lesion (Marsh 3) had significantly higher levels of soluble CD163 than patients with Marsh grade 2 lesions (P < 0.0004), with grade 1 lesions (P < 0.0001) and grade 0 lesions (P < 0.0001). Conclusions Measurement of soluble CD163 may be a useful method of monitoring the inflammatory lesion in coeliac disease.

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