Serum cytokine profiles in patients with Plasmodium vivax malaria: a comparison between those who presented with and without thrombocytopenia.

One of the peculiar features of Plasmodium vivax malaria in South Korea is the surprisingly high frequency of thrombocytopenia. The mechanism by which this malaria-related thrombocytopenia develops and its role in the pathology and progress of human infection with P. vivax have not yet been completely understood. In the present study, the serum cytokine profiles of cases of P. vivax malaria who presented with thrombocytopenia were compared with those of similar cases who did not have thrombocytopenia at presentation. The subjects were the 94 consecutive cases of P. vivax malaria who presented at five hospitals in South Korea (all near the Demilitarized Zone) between May 2000 and October 2002, 47 of whom had thrombocytopenia at presentation. When mean values and (S.E.) were compared, the thrombocytopenic patients were found not only to be generally older than the non-thrombocytopenic [25.3 (1.1) v. 21.3 (0.18) years; P < 0.001] but also to have presented with higher serum concentrations of aspartate aminotransferase [77.6 (16.6) v. 32.3 (7.4) U/litre; P < 0.0001], alanine aminotransferase [96.7 (19.0) v. 44.7 (12.0) U/litre; P = 0.0001], interleukin-1 [49.9 (7.4) v. 23.7 (5.1) pg/ml; P < 0.001], interleukin-6 [174.9 (26.4) v. 57.3 (14.6) pg/ml; P = 0.001], interleukin-10 [308.2 (39.6) v. 137.9 (23.1) pg/ml; P < 0.002] and transforming growth factor-beta [1134.3 (387.5) v. 416.6 (183.8) pg/ml; P < 0.0001], and higher levels of parasitaemia [4345.7 (966.6) v. 1443.8 (222.7) parasites/microl; P = 0.03). The non-thrombocytopenic patients, however, had relatively high total leucocyte counts [5.8 (0.24) v. 5.4 (0.66) leucocytes/nl; P = 0.03]. The thrombocytopenia associated with P. vivax malaria in South Korea therefore appears to be associated with elevated serum concentrations of both pro- and anti-inflammatory cytokines. To define the role of each cytokine in the development of thrombocytopenia during the course of acute P. vivax malaria, further prospective studies are needed.

Serologic and histopathologic study of Chlamydia pneumoniae infection in atherosclerosis: a possible pathogenetic mechanism of atherosclerosis induced by Chlamydia pneumoniae.

Chronic infection and inflammation have recently been implicated as important etiologic agents for atherosclerosis in general and, in particular, ischemic heart disease. Several agents have been suggested as possible candidates for the chronic inflammation including cytomegalovirus, Helicobacter pylori and Chlamydia pneumoniae. We hypothesized that a vascular infection with C. pneumoniae may induce a chronic inflammatory reaction in the host vascular tissue and activated inflammatory cells may express inflammatory mediators such as cyclooxygenase-2 (COX-2) and matrix metalloproteinases (MMPs). At first, we evaluated the relationship between C. pneumoniae infection and atherosclerosis indirectly by serologic study, and then, to confirm our hypothesis, we performed an immunohistochemical study of atherosclerotic plaques. The seropositive rate of anti-Chlamydia pneumoniae IgG was higher in the disease group (Group I, 59.8%, n = 254) than in the negative control group (Group III, 47.4%, n = 97) (p = 0.041), but the anti-Chlamydia pneumoniae IgA was not different in seropositivity between the two groups (Group I, 64.6%; Group III, 57.7%). The simultaneous seropositive rates of both IgG and IgA were 56.7% in Group I and 43.3% in Group III (p = 0.033). In subgroups without the conventional risk factors of atherosclerosis, these findings were more prominent. Furthermore, we performed immunohistochemical staining on the atherosclerotic aortic tissues obtained from patients that were seropositive to C. pneumoniae (n = 5), by using antibodies to C. pneumoniae, COX-2, and MMP-9. The immunoreactivity for COX-2 and MMP-9 increased in the atherosclerotic plaques itself, predominantly in the surrounding area of immunoreactive C. pneumoniae. These findings support our hypothesis and C. pneumoniae may participate in a pathogenetic mechanism for atherogenesis or progression of atherosclerosis. The present study may open a promising perspective concerning future therapeutic trials of chronic inflammation related atherogenesis under pathophysiological conditions.