Primary immune response to keyhole limpet haemocyanin following trauma in relation to low plasma glutamine

Abstract

SUMMARYSevere trauma can lead to a compromised immune response, thereby increasing susceptibility to infections. Here we will study to what extent these early changes in the immune status upon trauma affect a primary immune response to keyhole limpet haemocyanin (KLH). Because glutamine is the preferred respiratory substrate for immune competent cells and known to be depleted after trauma, we studied the immune status and the primary sensitization in relation to the glutamine plasma concentration in a group of severe trauma patients [injury severity score (ISS) > 17]. Trauma patients ( n = 31) were sensitized with KLH within 12 h after trauma; plasma glutamine concentrations and immune parameters were determined, after which KLH-specific immune responsiveness was evaluated on days 9 and 14. Low plasma glutamine concentrations were found after trauma. Significantly elevated numbers of granulocytes and CD14-positive leucocytes were found, whereas the HLA-DR expression on CD14-positive cells was significantly lower in trauma patients than in healthy controls. Trauma did not change the in vitro proliferative capacity of lymphocytes when cultured with glutamine; however, when lymphocytes were cultured without glutamine, trauma resulted in lower proliferation than healthy controls. Phytohaemagglutinin-(PHA)-induced interferon (IFN)-g and interleukin (IL)-10 production was significantly lower after trauma, whereas IL-4 production was not affected. KLH sensitization following trauma resulted in poor skin test reactivity and low in vitro KLH-induced lymphocyte proliferation compared to controls. In contrast, the development of anti-KLH IgM, IgG, IgA, IgG1, IgG2, IgG3 and IgG4 production on days 9 and 14 following trauma was not different from that in healthy controls. Major trauma was associated with a reduced cell-mediated immune response, correlating with low plasma glutamine concentrations, while no effects of trauma were found on the development of a primary humoral immune response.

Marine gastropod hemocyanins as adjuvants of non-conjugated bacterial and viral proteins

“…In their study concerning immuno toxicity Roth et al have shown that only the levels of KLH specific antibodies have been elevated in the group, immunized with KLH (50 mg/rat in aluminium hydroxide) compared to the control nontreated animals and there was no detectable difference between them in the following parameters: number CD4þ cells and lymphocyte count; development of germinal centers in Axillary lymph nodes and macrophage accumulation and granuloma formation/capsule in the site of the injection [26]. Boelens et al, examine the antibody response to KLH in healthy and trauma patients and did not find neither in the patients nor in the healthy controls anti KLH antibodies of the IgE-isotype [27].…”

Multiple vaccine and pyridostigmine bromide interactions in the common marmoset Callithrix jacchus: Immunological and endocrinological effects

“…KLH is recognised as a potent stimulator of T dependant humoral responsiveness and has been used to test immune function in many clinical situations, including severely traumatised patients [28]. There were robust antibody responses (IgM and IgG) against KLH in all treatment groups following boosting with that antigen.…”

Additive effects of exogenous IL‐12 supplementation and antibiotic treatment in infection prophylaxis

“…Trauma and major burns have been reported to result in diminished production of IL‐12, reduced Th1 responses, and decreased resistance to infection 10–21. IL‐12 has multiple biologic effects on T‐cell and natural killer (NK) cell functions.…”

“…Patients with traumatic open fractures or other serious injuries are vulnerable to infections, and it is generally agreed that the decreased resistance to infection is associated with abnormalities of both natural and adaptive immunity. Among those abnormalities is the loss of function of the T helper 1 (Th1) lymphocyte phenotype 10–21. Because Th1 cells are principal regulators of cell‐mediated immune response and the production of complement‐fixing antibodies,22 depressed function of this lymphocyte subset is believed to be related to reduced resistance to infection in injured patients 12, 16, 19, 21.…”