Substance P as an Immune Modulator of Anxiety

Abstract

Peripheral blood concentrations of the proinflammatory peptide substance P (SP) have been shown to increase in response to psychological anxiety in human subjects. In this study, we examined changes in SP levels in peripheral blood in response to the anxiety of a diagnostic medical procedure. The levels of SP were found to be higher in subjects with high initial anxiety as compared to subjects with low initial anxiety as measured on the Multiple Affect Adjective Checklist. Changes in the percentages of CD-8-expressing T lymphocytes were found to correlate with alterations in measures of anxiety as well as SP. These changes persisted for 3 days following the diagnostic procedure. The results of the study seem to indicate that SP may serve as a mediator in stress-induced immune reactions.

Selective Serotonin Reuptake Inhibitor and Substance P Antagonist Enhancement of Natural Killer Cell Innate Immunity in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

“…However, a different SP antagonist, L-759274, did demonstrate significant antidepressant effects (42). Similarly, elevated concentrations of cerebrospinal fluid (CSF) SP were found in both major depression and posttraumatic stress disorder (PTSD) (43), and we demonstrated that anxiety (44) and physiologic stress (45) are associated with elevated plasma levels of SP. Substance P is present within nerves of the autonomic nervous system and within the immune system, and the SP preferring receptor neurokinin-1R is highly expressed in brain regions regulating affective behavior and neurochemical responses to stress.…”

Measurement of Plasma-Derived Substance P: Biological, Methodological, and Statistical Considerations

“…SP was subsequently characterized as a neurotransmitter (31,32,33). Elevation of serum or plasma SP and/or its cell-associated receptor (NK-1R) has been observed by our laboratory and others in a variety of disorders, including inflammatory bowel disease (25); sickle cell crisis (29); depression and anxiety (4,15,20,28,37); rheumatological diseases (1,26); and infectious diseases, such as AIDS and respiratory syncytial virus (12,39), as well as in cancer (34,38). More recently, the role of SP in neurotransmission has been expanded to include a major role in the regulation of the immune response (27, 40; reviewed by Ho and Douglas [17]).…”

Novel Method for Determination of Substance P Levels in Unextracted Human Plasma by Using Acidification

“…Elevated levels of serum or plasma SP have been associated with disorders such as inflammatory bowel disease (16), sickle cell crisis (20), depression and anxiety (2,11,14,19,26), rheumatologic diseases (1, 17), infectious diseases (28), including human immunodeficiency virus (7, 8, 13), and cancer (24, 27). SP exerts its influence on immune responses through the induction of regulatory cytokines (3,18).Considerable variability has been reported for SP levels in similar biological fluids from healthy subjects and patients with diverse disease processes (5,7,8,9,11,12). Corbally et al (6) reported that endogenous human plasma-derived SP was reversibly and nonspecifically bound to both high-molecularmass proteins (Ͼ400,000 Da) and intermediate-molecularmass proteins (58,000 Da).…”

“…Its role as a neurotransmitter (21,22,23) includes regulation of immune responses (19). Elevated levels of serum or plasma SP have been associated with disorders such as inflammatory bowel disease (16), sickle cell crisis (20), depression and anxiety (2,11,14,19,26), rheumatologic diseases (1, 17), infectious diseases (28), including human immunodeficiency virus (7, 8, 13), and cancer (24, 27). SP exerts its influence on immune responses through the induction of regulatory cytokines (3,18).…”

“…Considerable variability has been reported for SP levels in similar biological fluids from healthy subjects and patients with diverse disease processes (5,7,8,9,11,12). Corbally et al (6) reported that endogenous human plasma-derived SP was reversibly and nonspecifically bound to both high-molecularmass proteins (Ͼ400,000 Da) and intermediate-molecularmass proteins (58,000 Da).…”