Abnormal regulation of inflammatory skin responses in male patients with chronic granulomatous disease

Abstract

A common characteristic of the response to infection seen in patients with chronic granulomatous disease (CGD) is an exaggerated and prolonged inflammatory response with frequent development of draining lymph nodes and granuloma formation. Recent reports of several CGD patients with minor but significant in vitro abnormalities of cellular and humoral components of neutrophil chemotactic responses would predict lessened responses to inflammatory stimuli. The following studies were, therefore, performed to assess in vivo inflammatory responses in patients with CGD. Twenty-four-hour Rebuck skin-window procedures were performed on eight patients (five male and three female) with CGD and on ten volunteers. The windows were changed 1, 3, 5,8, 12, and 24 h after the abrasion. Quantitation of the skin windows was performed with the assistance of a microscopeimage analyzer computer facility. Neutrophil accumulation into skin windows was normal in CGD patients throughout the first 5 h. However, during the 8-to 24-h period, when neutrophils characteristically disappear from normal inflammatory responses and are replaced by monocytes, there was abnormal persistence of PMN at the inflammatory foci in male but not in female CGD patients (P< 0.05 for the comparison of the rates of decline of PMN, from hour 8 to hour 24, in five male CGDs and in 10 normals). Monocyte recruitment was normal. In one CGD male, the abnormal skin-window response was normalized while he was receiving white cell transfusions. The data indicate that there is an abnormal “turn off” of the acute inflammatory response in male CGD patients and support a modulatory role for products of oxidative metabolism on the inflammatory response. In addition, they indicate that the mild in vitro defect in neutrophil chemotaxis is not associated with a depressed, acute inflammatory response in vivo and, therefore, does not explain the increased susceptibility of CGD patients to certain infections.