With advances in medical research as a catalyst, physicians now manage patients with multiple, concurrent insults and complicated disease processes. Paradoxically, many advanced interventions prolong patients’ lives but also expose the patient to additional inflammatory insults. Examples of these sequential insults would be development of sepsis after initial treatment of burn injury or aspiration of stomach contents during anesthesia for emergency appendectomy. It has been hypothesized that the initial insult will actually prime the immune system for an exaggerated inflammatory response to a second insult. Our research focuses on the complex immune responses associated with sequential inflammatory insults involving sepsis. One of our pursuits is to understand the effects of compartmentalization of inflammatory insults, i.e. the effect lung inflammation has on the host’s response to inflammation elsewhere in the body and vice versa. In addition, we seek to understand how the timing and/or the relative strength of sequential inflammatory insults regulates the host’s immune status and eventual outcome.

In our studies of sequential inflammatory insults, we examine the activity of several inflammatory mediators as the factors that either prime or trigger the body’s immune responses. We use a murine model of bacterial peritonitis (cecal ligation and puncture) followed by a direct lung insult. This model is used to study several aspects of the responses that occur during sepsis. The individual and combined effects of the pro and anti-inflammatory cytokines are a major focus of this research. With special interest, we also examine the role of the CXC chemokines on neutrophil recruitment to the local site of inflammation as well as to distant compartments. In addition, we are developing pneumonia and hemorrhage models to study the pathogenesis of clinically relevant inflammatory disease.

Due to the major role that the neutrophil plays in both sepsis and lung injury, we are interested in the effects of sequential insults on the function of this cell, including receptor expression, chemotactic responses and production of superoxide radicals. To further understand factors affecting neutrophil recruitment, we also examine the differential in vitro production of CXC chemokines (KC, MIP-2α, LIX) by primary macrophages and fibroblasts from the murine lung. New studies will examine the interaction of neutrophils and dendritic cells in sepsis.

Our laboratory also has an interest in research related to laboratory animal medicine. We continue to pursue studies in mice concerning stress related to routine blood collection and temperature monitoring in mice, selection of humane endpoints in shock research and monitoring the immune effects of environmental endotoxin.

Selected publications:
Nemzek JA, Xiao HY, Minard AE, Bolgos GL, and Remick, DG. Humane Endpoints in Shock Research. Shock, (1): 17-25, 2004.

Nemzek JA, Ebong SJ, Kim J, Bolgos GL, Remick DG. KGF pretreatment is associated with decreased MIP-2a concentrations and reduced neutrophil in acid aspiration lung injury. Shock, 18 (6):501-6, 2002.

Nemzek JA, Bolgos GL, Williams B, Remick G. Differences in normal values for murine white blood cells and other hematological parameters based on sampling site. Inflamm Res 50:523-527, 2001.

Nemzek JA, Siddiqui J, Remick DG. Development and optimization of cytokine ELISA’s using commercial antibody pairs. J Immunol Methods 255 (1-2):149-57, 2001.

Kim J, Merry MC, Nemzek JA, Bolgos GL, Siddiqui J, Remick DG. Eotaxin represents the principal eosinophil chemoattractant in a novel murine asthma model induced by house dust containing cockroach allergens. J Immunol 2001 167: 2808-2815.

Call, DR, Nemzek JA, Ebong SJ, Bolgos GL, Newcomb DE and DG Remick.
Ratio of local to systemic chemokine concentrations regulates neutrophil recruitment. Am J Pathol 158:715-721, 2001.