Healthy Controls, Stress, & Inflammation
In response to the test anxiety many student subjects, who anticipate oral or professional examination, also experience symptoms of headaches, sore throats, fatigue, nausea, earaches, and some intestinal discomfort (Lacey et al., 2000). When compared with 6-8 week pretest cortisol levels, testing plasma cortisol levels are significantly elevated and then gradually decline in the two-week period following an examination. Plasma ACTH test levels are significantly higher than 6-8 week pretest levels and do not gradually decline at two week post-examination. Although IL-1β levels do not vary over the pretest-test-posttest periods, lymphocyte proliferation levels are significantly lower in stressed subjects and return to pretest levels two weeks later (Lacey et al., 2000). Other findings support immune elevations in response to the stress of anticipated examination immediately prior to and during the testing session. Plasma increases in the proinflammatory cytokine interferon gamma (IFN-γ) and IL-6 as well as anti-inflammatory cytokine interleukin (IL-10) are noted as well as increases in the IFN-γ/IL-10 testing ratio (Marshall et al., 1998) that decline following an examination. In addition, students self-described as very stressed present significant plasma cytokine increases in tumor nucrosis factor alpha (TNF-α), IFN-γ, IL-1Ra (Maes et al., 1998) along with increases in the circulating alpha two adrenergic a receptor (α2-AR) as reflected by increases in α2-AR Bmax values (Maes et al., 2002). Test anxiety and test taking decrease immune mediators of IL-2, IFN-γ, IL-1β and natural killer cells (NK) during the post-testing period along with concomitant increases in IL-1Ra and IL-10 (Uchakin et al., 2001) in LPS cultures. Decreasing proinflammatory levels reflect the resolving of initial proinflammatory increases with post-test.
Intellectually challenging mental tasks coupled with task-irrelevant stress-inducing interferences stimulate plasma lymphocyte proliferation, which is suppressed by high doses of dexamethasone treatment. Blood sample assays taken immediately after mentally challenging tasks produce anti-inflammatory IL-4 decreases; whereas, inflammatory IL-6 assays demonstrate decreases 15 and 30 minutes after each task challenge (Peters et al., 1999) again suggesting post-test attempts at resolving prior inflammatory response. Increases in plasma concentrations of IL-6, IL-1Ra, and TNF-α are positively associated with increases in systolic blood pressure, diastolic blood pressure, and heart rate, respectively. In addition, a positive relationship between both IL-6 and IL-1Ra reaches statistical significance at 45 minutes post-test (Steptoe et al., 2001). Women tend to present greater stress-induced increases of IL-6 and IL-1Ra, while men demonstrate greater increases in TNF-α (Steptoe et al., 2002).
Public speaking stress produces increases in heart rate, blood pressure, plasma concentrations of adrenaline and noradrenaline, CD16+/CD56+ natural killer cell activity (NKCA), and IFN-γ in PHA cultures that return to baseline values one hour after the task (Jacobs et al., 2001; Larson et al., 2001). The stress of public speaking produces increases in lipopolysaccharide (LPS) expression of IL-6 in blood drawn at the time of testing (Goebel et al., 2000) that can be decreased (or suppressed) by dexamethasone (DEX) treatment (Rohleder et al., 2001).
Parents of cancer patients reporting psychological distress in response to their children’s illnesses present lower LPS-induced levels of IL-6 and greater average levels of TNF-α when compared with parents of healthy children. IL-6 levels show significantly less dexamethasone suppression of IL-6 production, suggesting chronic negative feedback inhibition to the stress of having a sick child (Miller et al., 2002). Blunted DEX suppression is a characteristic neurohormonal response of depressed patient populations (discussed further in section 1.46).
In summary the immune system is normally activated in response to acute psychological stress and is quickly regulated upon the termination of stress in healthy individuals. The mechanism underlying stressed-induced immune activation remains elusive. The HPA and norepinephrine and epinephrine systems (Elenkov et al., 2000) play indirect roles in engaging immune reactivity to psychological stress.
References
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