Modification of the antitumor action of Corynebacterium parvum by stress.

Social grouping and isolation of mice, in the presence of an acute stressor, were found to differentially affect the antitumor action of the immunological adjuvant Corynebacterium parvum. Socially grouped DBA/2j mice were injected intradermally with P815 mastocytoma ascites cells. Half the mice had a threshold dose of C. parvum admixed with the P815 cells. Half the mice in each of those conditions were given acute, inescapable electric footshock. In a second experiment, the stressed mice were socially isolated prior to the acute stress. Tumor growth itself was not affected by the stress procedures. C. parvum inhibited tumor growth in non-stressed and socially isolated, stressed mice. However, social grouping selectively negated the C. parvum effect resulting in tumor growth and mortality equivalent to mice not given the adjuvant. Psychological factors may be important to the development of concomitant immunity and the efficacy of immunotherapies.

Inhibition of in vivo neutrophil accumulation by stress. Possible role of neutrophil adherence.

Psychological stress results in neural and endocrine changes which can alter various aspects of the immune system. However, the effects of stress on inflammation has not received much attention despite the fact that stress hormones, such as the corticosteroids, are known to reduce inflammation. The present study extends a previous finding that stress itself can reduce inflammation. In the first experiment, zymosan was injected into an air pouch on the dorsum of F344 rats. Half of these rats then received three hours of inescapable, intermittent, electric foot shock as a stressor. The other half of the injected rats served as nonstressed controls. A third group were given air pouches but no zymosan. Fewer neutrophils accumulated at the inflammatory site of stressed rats as compared to nonstressed control rats. However, phagocytosis of zymosan by air pouch neutrophils was higher in stressed rats. Peripheral perfusion was not altered significantly by shock, but vascular permeability was reduced in stressed rats. The effects of stress on peripheral blood leukocytes of rats not injected with zymosan was investigated. It was found that while peripheral blood monocytes and lymphocyte numbers were decreased by stress, neutrophils were not decreased. Increased neutrophil adherence was found in stressed rats. Additionally, in the presence of endotoxin, neutrophils from stressed rats did not increase their adherence as much as those of control rats. The increased adhesiveness of neutrophils in stressed animals may account for the diminished inflammatory response in the shocked rats.

Splenomegaly and other hematological parameters in the socially dominant mouse.

Within a social dominance hierarchy, subordinate mice show hematological changes such as increased erythropoiesis and splenomegaly. The present experiment demonstrates similar findings for the unwounded dominant mouse. In addition, total serum protein, serum albumin and plasma fibrinogen were measured. Male DBA/2j mice were placed into social triads for three 24 hr periods. The resultant dominant and subordinate mice were compared with isolated control mice. Splenomegaly, thymus involution, decreased hematocrit, and increased fibrinogen levels were found in dominant mice. Subordinate mice demonstrated the same changes to a greater extent, as well as an increased reticulocyte count. Only dominant mice showed a reduction in total serum protein. Wounding-independent processes must be involved in these cellular and non-cellular hematological effects of psychosocial stress.

Systolic blood pressure during the formation of a social dominance hierarchy in C57BL/6j mice.

Housing male mice in social groups typically results in social dominance hierarchies and elevated systolic blood pressures. An exception to this pattern occurs in the C57BL/6j inbred mouse strain. C57BL/6j male mice, when handled prior to the experiment, tend to display neither social dominance hierarchies nor systolic hypertension. In the present experiment, we found that when C57BL/6j males compete for social dominance, as indicated by wounding, they also show elevations in systolic pressure. The association of social hierarchy and systolic pressure elevation can be found not only in aggressive mouse strains, but also within the more pacific C57BL/6j strain when it is exposed to competition.