Donald A. Cohen, Ph.D.
Professor

Microbiology and Immunology
Markey Cancer Center

Phone:
(859) 323-5131

Fax:
(859) 257-8994

E-mail:
dcohen@uky.edu

Weblink:
http://jenner.mi.
uky.edu/index4.htm

Chronic inflammation in the lungs can be caused by a variety of factors, including infectious agents, autoimmunity, environmental pollutants and therapeutic modalities. Regardless of the cause, persistent inflammation can lead to the development of structural changes in the lung architecture that can affect breathing capacity. Research in this laboratory is focused on understanding immunological mechanisms which lead to structural changes in the lungs during chronic inflammatory reactions.

1. Interstitial pneumonitis Following Bone Marrow Transplantation. The clinical success rate of bone marrow transplantation has increased steadily over the last several decades. In spite of these successes, infectious and noninfectious pulmonary complications and graft-versus-host disease remain the greatest threat to survival after transplant. Mortality from interstitial pneumonitis following bone marrow transplantation has been reported as high as 85%. Idiopathic interstitial pneumonitis, which recently has been termed idiopathic pneumonia syndrome (IPS) accounts for as many as 50% of the total cases of interstitial pneumonitis after bone marrow transplantation. We have hypothesized that radiation treatment prior to bone marrow transplanation generates oxygen radicals in the lung which leads to inappropriate expression of MHC class I and class II molecules and costimulator molecules on lung cells such as endothelial cells, epithelial cells and fibroblasts. Increased expression of these molecules increases the chance that alloreactive T cells in donor bone marrow will begin to attack lung tissue. Using a murine model of IPS after bone marrow transplantation, we are evaluating conditions of lung irradiation which promote the induction of IPS, such as changes in expression of histocompatibility and costimulatory molecules, and radiation-induced cytokines. We are also evaluating the immunosuppressive capacity of resident lung macrophages in protecting the lung from the development of IPS.
2. Interstitial Pneumonitis of AIDS. Pulmonary complications are responsible for significant morbidity and mortality among HIV⁺ individuals. In addition to pulmonary infections, noninfectious complications of the lungs also are frequently observed during both AIDS and AIDS-related complex. Idiopathic interstitial pneumonitis (IP) has been shown to be a major noninfectious pulmonary complication of HIV in both adults and children. Our research group has developed a murine model of immunodeficiency-associated interstitial pneumonitis, using a murine retrovirus model of AIDS induced by the LP-BM5 retrovirus. Mice infected with this retrovirus develop chronic lung inflammation that is associated with persistent synthesis of proinflammatory cytokines. Current studies are focused on evaluating the function of IL-10 and its receptor, IL-10R, in downregulating pulmonary inflammation in this animal model of AIDS-associated pneumonits.
   

Research Publications/Presentations

Shankar, G., J.S. Bryson, C. Darrell Jennings, Peter E. Morris and D.A. Cohen. Idiopathic Pneumonia Syndrome in Mice Following Allogeneic Bone Marrow Transplantation. Am J Respir Cell Mol Biol 18:235-42, 1998.

Fitzpatrick, E.A., Avdiushko, M., Kaplan, A.M. and Cohen, D.A. Role of virus replication in a murine model of AIDS-associated interstitial pneumonitis. Exp Lung Res 25:647-661, 1999.

Shankar, G., J.S. Bryson, C.D. Jennings, A. M. Kaplan and D. A. Cohen. Idiopathic pneumonia syndrome following allogeneic bone marrow transplantation in mice: the role of pre-transplant radiation conditioning. Amer J Resp Cell Mol Biol 20:1116-1124, 1999.

Fitzpatrick, E.A., Avdiushko, M., Kaplan, A.M. and Cohen, D.A. Role of T cell subsets in a murine model of AIDS-associated interstitial pneumonitis. Exp Lung Research 25:671-687, 1999.