Cytokines in portopulmonary hypertension

I wish to raise some questions regarding the paper of Benjaminov et al on portopulmonary hypertension in decompensated cirrhosis with refractory ascites (Gut 2003;52:1355–62).

Although the role of endothelin-1 in portopulmonary hypertension has been suggested by many clinicians and is timely, as well as clinically important, issues remain concerning the limited number of patients (n = 10 portopulmonary patients) presented in this study. Furthermore, it is very difficult to demonstrate or hypothesise a role of endothelin-1 in portopulmonary hypertension without measuring gradients of endothelin-1 over the pulmonary and portal vascular beds. Without these data, how do they know where the increased levels of endothelin-1 came from?

Furthermore, why did the authors not analyse the role of circulating cytokines, such as interleukin 6 and interleukin 1β which are implicated in the pathogenesis of pulmonary hypertension? We found high plasma concentrations of endothelin-1 and in particular interleukin-6 in 15 patients affected by portopulmonary hypertension and in a group of 20 patients with primary pulmonary hypertension (endothelin-1, 5.26 (3.5) v 5.69 (1.4) pg/ml; interleukin 6, 9.1 (3.1) v 6.6 (4.4) pg/ml, respectively) compared with a group of 30 cirrhotics with ascites (endothelin-1, 1.79 (0.8); interleukin 6, 3.43 (2.7)). Our data suggest that endothelin-1 and in particular interleukin 6 show similar plasma concentrations in portopulmonary hypertension and primary pulmonary hypertension and could play a part in the pathogenesis of these diseases.¹