Altered Cytokine Production and Impaired Antimycobacterial Immunity in Protein-Malnourished Guinea Pigs

Abstract

Protein malnutrition leads to multiple detrimental alterations of host immune responses to mycobacterial infection. In this study, we demonstrated that splenocytes from low-protein (LP) guinea pigs vaccinated 6 weeks previously with attenuated Mycobacterium tuberculosis H37Ra failed to control the accumulation of virulentM. tuberculosis H37Rv in cocultured autologous peritoneal macrophages, despite the fact that they were able to control the accumulation of virulent tubercle bacilli in cocultured syngeneic peritoneal macrophages from normally nourished guinea pigs as successfully as did those from high-protein (HP) counterparts. Vaccine-induced growth control of virulent M. tuberculosisH37Rv in these cocultures appeared to be mediated by CD4 lymphocytes but not CD8 cells. Tuberculin (purified protein derivative [PPD])-induced lymphoproliferation was markedly impaired in vaccinated LP guinea pigs, and the depletion of CD4 lymphocytes significantly decreased lymphocyte proliferation whereas CD8 cell depletion did not. Protein malnutrition also impaired the abilities of cells from vaccinated LP guinea pigs to produce cytokines, including interferon, tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β), in response to PPD, despite the demonstration of higher serum levels of TNF-α and TGF-β after an intravenous injection of PPD into LP guinea pigs. In contrast, peritoneal macrophages from protein-malnourished guinea pigs produced a higher level of TGF-β 4 days after infection in vitro with M. tuberculosis H37Rv than did those from protein adequate controls. These results suggest that dietary protein malnutrition impairs vaccine-induced resistance to M. tuberculosis, in part, by altering the cytokine profile to favor macrophage deactivation.

Low Protein Intake Is Associated With Impaired Titanium Implant Osseointegration

“…Thus, both mechanisms (i.e., increased resorption and decreased formation) are likely to impair implant osseointegration. In protein restriction-induced bone resorption, (11) bone resorptionstimulating cytokines, such as TNF-␣, (11,(31)(32)(33) or sex hormone deficiency could be implicated. (11) With the agerelated decline in renal function, blood pH slightly decreases, possibly in relation with excess dietary pro- tein.…”

Molecular characterization of guinea ‐ pig (Cavia porcellus) CD8α and CD8β cDNA

“…In general, the guinea pig serves as an ideal non‐primate model as it is hormonally and immunologically more similar to humans (13) than the rodent models. In particular, a guinea pig model for tuberculosis has been shown to have delayed type hypersensitivity and increased necrosis in lungs after Mycobacteria tuberculosis exposure similar to that seen in humans (14–16). Similarly, both genital and ocular infection of guinea pigs with the Chlamydia psittaci agent of guinea pig conjunctivitis results in a disease that parallels that seen in human and primates with respect to both infection course and pathologic response (17).…”

Effects of maternal protein or energy restriction during late gestation on immune status and responses to lipopolysaccharide challenge in postnatal young goats1

“…In rats, moderate dietary PR during gestation impaired offspring thymocyte proliferation at birth and thymic and spleen lymphocyte proliferation at weaning (Calder and Yaqoob, 2000). Malnutrition decreased T cell function, cytokine production, and the ability of lymphocytes to respond appropriately to cytokines (Dai and McMurray, 1998). It was also reported that T lymphocytes from malnourished infants were shortlived and dysfunctional .…”