Cohabitation with a sick partner increases allergic lung inflammatory response in mice

Abstract

The bidirectional relationship between the nervous system and the immune system is relevant for homeostatic organism maintenance. Studies from our laboratory showed that 14days of cohabitation with a sick partner (injected with Ehrlich tumor cells-TAE) produced behavioral, neurochemical, endocrinological and immunological changes. This study analyzes the effects of cohabitation with an Ehrlich tumor-bearing animal on ovalbumin (OVA)-induced lung inflammatory response in mice. Pairs of male mice were divided into three groups: naïve, control and experimental. Animals of the naïve group were kept undisturbed being used for the assessment of basal parameters. One animal of each experimental and control pair of mice was immunized with OVA. On ED(0), these OVA-immunized animals received an OVA booster. At this day (D(0)) the experimental mice that were kept undisturbed were inoculated with 5×10(6) Ehrlich tumor cells; their immunized cage-mates were then referred as to CSP ("companion of sick partner"). The undisturbed mice of each control pair were i.p. treated on D(0) with 0.9% NaCl; their sensitized cage-mates were subsequently referred as CHP ("companion of health partner"). The OVA challenge was performed on CSP and CHP mice on ED(12) and ED(13); blood and tissue collection were performed on ED(14). Fourteen days after cohabitation, in comparison to the CHP mice, the CSP mice displayed the following: (1) an increased number of eosinophils and neutrophils in the BAL, (2) a decreased bone marrow cell count, (3) increased levels of IL-4 and IL-5 and decreased levels of IL-10 and IFN-γ in the BAL supernatant, (5) increased levels of IgG1-OVA, decreased levels of IgG2a-OVA and no changes in OVA-specific IgE in the peripheral blood, (6) increased expression of L-selectin in the BAL granulocytes, (7) decreased tracheal reactivity to methacholine measured in vitro, (8) no changes in plasma corticosterone levels and (9) increased levels of plasmatic noradrenaline. These results suggest that allergic lung inflammatory response exacerbation in CSP mice is a consequence of the psychological stress induced by forced cohabitation with the sick partner. Strong involvement of the sympathetic nervous system (SNS) through adrenaline and noradrenaline release and a shift of the Th1/Th2 cytokine profile toward a Th2 response were considered to be the mechanisms underlying the cell recruitment to the animal's airways.

Assessment of social behavior directed toward sick partners and its relation to central cytokine expression in rats

“…For example, several studies have demonstrated suppression of social behavior directed toward sick conspecifics [17]. Recent studies have also shown that when normal mice are housed with tumor-bearing conspecifics, the “healthy” mice develop immunological aberrations indicative of allergic hypersensitivity [18]. Very little is known, however, regarding the impact of interaction with a sick social partner on expression of central expression of pro-inflammatory cytokines and other aspects of neuroimmune function.…”

Beta-Adrenergic Blockade Decreases the Neuroimmune Changes in Mice Induced by Cohabitation with an Ehrlich Tumor-Bearing Cage Mate

“…Physical and psychological stressors are known to induce endocrine [12] , neurochemical [13] , and immune [8] changes similar to the changes currently reported in mice after cohabitation with a tumor-bearing cage mate. The lack of changes in the serum corticosterone levels in the companions of ETB mice [10,11,14] led us to suggest that the final neural link between the neuroimmune impairments observed in companions of the ETB mice involves catecholamine release and/or CNS catecholaminergic activation as a consequence of the psychological stress imposed by the forced housing condition. Changes in catecholamine levels after stress were reported to modify the cytokine network [15] and cytokines are known to modulate the activity of immune cells [16] and the animal's resistance to diseases [17] .…”

“…Although the overall neuroimmune outcomes of cohabitation in companions of ETB mice have been extensively reported [10,11,14,22,23] , we must determine whether catecholamine release and SNS activation are indeed related to the neuroimmune effects on the development of behavioral and neutrophil alterations reported to be caused by the housing condition. Therefore, the purpose of the present study was to determine the extent to which catecholamines participate in these effects by employing β-AR blocking agents as pharmacological tools.…”

<b>Efeitos da hiperprolactinemia sobre a inflamação alérgica pulmonar em ratos Wistar</b>

“…A IL-4 conduz à diferenciação das células Th0 naive a células Th2 no curso da inflamação alérgica pulmonar (HAMASATO et al, 2014). É por isso que no experimento 3, os grupos asmáticos como controle, veículo e domperidona apresentaram níveis altos dessa citocina, com relação ao grupo naive, que não tinha processo inflamatório pulmonar nenhum.…”

“…O recrutamento e migração de eosinófilos dentro da área inflamada após o desafio ao antígeno é controlado por citocinas, quimiocinas e mediadores inflamatórios. As respostas imunes alérgicas são unidas ao desbalançe Th1/Th2 com um aumento no perfil de citocinas Th2 (HAMASATO et al, 2014).…”