Mice depleted of alphabeta but not gammadelta T cells are resistant to mortality caused by cecal ligation and puncture.

The present study was undertaken to determine whether the mice depleted of alphabeta or gammadelta T cells show resistance to acute polymicrobial sepsis caused by cecal ligation and puncture (CLP). T-cell receptor beta knockout (betaTCRKO) and T-cell receptor delta knockout (deltaTCRKO) mice were used. An additional group of mice was treated with an antibody against the alphabeta T-cell receptor to induce alphabeta T-cell depletion; a subset of alphabeta T cell-deficient mice was also treated with anti-asialoGM1 to deplete natural killer (NK) cells.

Effect of transforming growth factor-beta neutralization on survival and bacterial clearance in a murine model of Pseudomonas aeruginosa burn wound infection.

Transforming growth factor-beta (TGF-beta), a cytokine with anti-inflammatory properties, may contribute to postburn immunosuppression. This study was designed to determine whether neutralizing TGF-beta in burned mice could improve resistance to infection. C57BL/6J mice received a 35% TBSA flame burn under isoflurane anesthesia.

Endotoxin priming improves clearance of Pseudomonas aeruginosa in wild-type and interleukin-10 knockout mice.

Endotoxin (lipopolysaccharide [LPS]) tolerance is an altered state of immunity caused by prior exposure to LPS, in which production of many cytokines, including gamma interferon (IFN-gamma) and interleukin-12 (IL-12), are reduced but secretion of the anti-inflammatory cytokine IL-10 is increased in response to a subsequent LPS challenge. This pattern of cytokine production is also characteristic of postinflammatory immunosuppression. Therefore, we hypothesized that LPS-primed mice would exhibit an impaired ability to respond to systemic infection with the opportunistic pathogen Pseudomonas aeruginosa.

Glucan phosphate treatment attenuates burn-induced inflammation and improves resistance to Pseudomonas aeruginosa burn wound infection.

These studies evaluated the effects treatment with glucan phosphate, a soluble polysaccharide immunomodulator, on the inflammatory response induced by burn injury and on resistance to Pseudomonas aeruginosa burn wound infection. Mice were exposed to 35% total body surface area burns and were resuscitated with lactated Ringer's (LR) solution alone or LR supplemented with glucan phosphate (40 mg/kg). Glucan phosphate treatment attenuated burn-induced expression of interleukin (IL)-1beta, IL-6, and IL-10 mRNAs in spleen, lung, and heart.

Enhancement of dendritic cell production by fms-like tyrosine kinase-3 ligand increases the resistance of mice to a burn wound infection.

Fms-like tyrosine kinase-3 ligand (Flt3L) is a hemopoietic cytokine that stimulates the production of dendritic cells. This study evaluated the ability of Flt3L-enhanced dendritic cell production to increase the resistance of mice to a burn wound infection with Pseudomonas aeruginosa, a common source of infections in burn patients that have impaired immunity and are susceptible to opportunistic microorganisms. Treatment of mice with Flt3L for 5 days caused a significant increase in dendritic cell numbers in the spleen and significantly increased survival upon a subsequent burn wound infection.

Mice depleted of CD8+ T and NK cells are resistant to injury caused by cecal ligation and puncture.

We previously showed that beta 2 microglobulin knockout mice depleted of NK cells by treatment with anti-asialoGM1 (beta2MKO/alphaAsGM1 mice) are resistant to sepsis caused by cecal ligation and puncture (CLP). beta2MKO mice possess multiple immunological defects including depletion of CD8+ T cells. This study was designed to determine the contribution of CD8+ T and NK cell deficiency to the resistance of beta2MKO/alphaAsGM1 mice to CLP-induced injury.