Stress May Restrain the Immunostimulatory Effects of Interleukin-12

Stress May Restrain the Immunostimulatory Effects of Interleukin-12

A new study published in the journal Brain, Behavior, and Immunity suggests that chronic stress exposure can abolish the effects of immunostimulatory treatments such as the administration of interleukin (IL)-12, which is independent from the stress effects on baseline immune measures.

Type 1 T-helper (Th)1 and proinflammatory cytokines are major activators of Th1-dependent cellular immunity, and anti-tumor effects of IL-12 are reported in various animal models.

Despite these promising beneficial effects of IL-12 in the context of cancer immunotherapy and surgery, the use of IL-12 in the clinical settings, however, has yielded rather limited results. A factor that may contribute to this discrepancy is the environmental and psychological state that characterizes cancer patients.

In the Brain, Behavior, and Immunity study, Ben Levi and colleagues from Neuroimmunology Research Unit, Tel-Aviv University, Israel, reveal a new mechanism by which stress can affect immunoregulation. They found that exposure to behavioral stress before IL-12 administration diminished the increase in NK number and activity caused by IL-12 in non-stressed animals. This was evident in the marginalizing-pulmonary immune compartment, which is critical for resisting lung metastases.

In addition, in the MADB106 experimental metastases model, the administration of IL-12 efficiently improved MADB106 lung clearance, but continuous stress alongside IL-12 treatment markedly reduced these beneficial effects.

The authors propose that continuous stress affects the ability of IL-12 to cause immunostimulation, irrespective of affecting baseline levels of the measured outcome. According to the authors the neuroendocrine-immune mechanisms behind this phenomenon are yet unknown. It is likely however, that stress may disrupt the efficacy of IL-12 by mounting a Th2 response before the beginning of IL-12 treatment  and thus, consequently hindering the ability of IL-12 to induce an effective Th1 response, which is critical for proper activation of cellular immunity.

Since stress responses in patients may include a continuous systemic elevation of stress hormones that, as shown herein, may disrupt the efficacy of the immunostimulatory treatment, this study may have important clinical implications. Therefore, further insights and studies along these lines may lead to the development of potential interventions that could prevent the disruption to immunostimulatory treatment.

SOURCE: Brain Behav Immun, 2011 25:727. Epub 2011 Jan 28.

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Source: Cover Image: Crystal structure of human Interleukin-12. For the original data, see: Yoon, C., Johnston, S.C., Tang, J., Stahl, M., Tobin, J.F., Somers, W.S. Charged residues dominate a unique interlocking topography in the heterodimeric cytokine interleukin-12. EMBO J. v19 pp.3530-3541, 2000. Credit: Wikimedia Commons.

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