Am. J. Respir. Crit. Care Med., Volume 164, Number 7, October 2001, 1186-1191

Spectrum of CD4 to CD8 T-Cell Ratios in Lymphocytic Alveolitis Associated with Methotrexate-induced Pneumonitis

CLAIRE FUHRMAN, ANTOINE PARROT, MARIE WISLEZ, HÉLÈNE PRIGENT, VÉRONIQUE BOUSSAUD, JEAN-FRANÇOIS BERNAUDIN, CHARLES MAYAUD, and JACQUES CADRANEL

Service de Pneumologie et de Réanimation Respiratoire, Hôpital Tenon, AP-HP, Paris; Service de Pneumologie Centre Hospitalier Intercommunal de Créteil, Créteil; Laboratoire de Biologie et d'Immunopathologie Pulmonaire UPRES EA 15³ 1, Université Paris VI, UFR Saint-Antoine, Paris; Service d'Histologie et de Biologie Tumorale, Hôpital Tenon, AP-HP, Paris, France

The present study was conducted to confirm the presence of severe lymphocytic alveolitis and to determine the factors responsible for the very different alveolar CD4 to CD8 T-cell ratios (CD4/ CD8) described in methotrexate-induced pneumonitis (MTX-pneumonitis). Clinical and radiologic findings, as well as bronchoalveolar lavage (BAL) data, including CD4 and CD8 subset analysis, were retrospectively reviewed for patients hospitalized between 1985 and 2000 for MTX-pneumonitis. BAL cell counts from patients with MTX-pneumonitis (cases) were compared with those from patients receiving MTX but who did not have evidence of MTX toxicity (MTX-exposed patients) and those from healthy subjects (control subjects). Nineteen BAL were performed in 14 consecutive cases of MTX-pneumonitis. MTX was given for various underlying diseases. All cases presented a subacute diffuse interstitial pneumonitis that recovered, with MTX discontinuation and/or initiation of adjunctive steroid therapy. At the time of diagnosis, BAL cell counts in MTX-pneumonitis indicated severe lymphocytic alveolitis when compared with MTX-exposed patients and control subjects and moderate neutrophil alveolitis compared with control subjects. The lymphocytic alveolitis resulted from an increase in both CD4 and CD8 lymphocyte cell counts. Nevertheless, alveolar CD4/ CD8 T-cell ratios ranged from 0.4 to 9.6. CD4/CD8 values correlated positively with lymphocyte counts but negatively with time elapsed between last MTX administration and BAL and with steroid cumulative dose received by the patients. Severe lymphocytic alveolitis was confirmed in our series of MTX-pneumonitis. The between-patient variation in CD4/CD8 T-cell ratios may reflect the large range of time intervals between last MTX administration and BAL evaluation and the use of adjunctive steroid therapy.

This article has been cited by other articles:

				S Inokuma, H Kono, Y Kohno, K Hiramatsu, K Ito, K Shiratori, J Yamazaki, H Nakayama, H Shoda, and Y Tanaka Methotrexate-induced lung injury in patients with rheumatoid arthritis occurs with peripheral blood lymphocyte count decrease. Ann Rheum Dis, August 1, 2006; 65(8): 1113 - 1114. [Full Text] [PDF]

				L. Bruckner, F. Gigliotti, T. Wright, A. Harmsen, R. H. Notter, P. Chess, Z. Wang, and J. Finkelstein Pneumocystis carinii infection sensitizes lung to radiation-induced injury after syngeneic marrow transplantation: role of CD4+ T cells Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1087 - L1096. [Abstract] [Full Text] [PDF]

				V. Saravanan and C. A. Kelly Reducing the risk of methotrexate pneumonitis in rheumatoid arthritis Rheumatology, February 1, 2004; 43(2): 143 - 147. [Full Text] [PDF]

				D. Steiger, L. Bubendorf, M. Oberholzer, M. Tamm, and J.D. Leuppi Ciprofloxacin-induced acute interstitial pneumonitis Eur. Respir. J., January 1, 2004; 23(1): 172 - 174. [Abstract] [Full Text] [PDF]

				M. J. TOBIN Tuberculosis, Lung Infections, Interstitial Lung Disease, and Socioeconomic Issues in AJRCCM 2001 Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 631 - 641. [Full Text] [PDF]