Interleukin-1beta sensitizes abdominal visceral afferents of cats to ischaemia and histamine.

1. Activation of abdominal splanchnic visceral afferents during mesenteric ischaemia induces visceral pain and evokes excitatory cardiovascular responses. Previous studies have shown that interleukin-1beta (IL-1beta) concentration is increased locally in tissues during ischaemia and reperfusion. Local administration of IL-1beta sensitizes somatic afferents to mechanical, thermal and chemical stimulation. Therefore, we hypothesized that IL-1beta stimulates or sensitizes splanchnic visceral afferents to ischaemia and to the action of chemical stimuli such as histamine. 2. The concentration of IL-1beta in mesenteric lymph and portal venous plasma in anaesthetized cats was measured with an enzyme-linked immunosorbent assay before, during and after 10 min of abdominal ischaemia. The level of IL-1beta was significantly increased during ischaemia in lymph, but not in plasma. 3. Discharge activity of single-unit abdominal visceral C fibre afferents was measured from the right thoracic sympathetic chain. Ischaemically sensitive C fibre afferents were identified according to their response to 5-10 min of abdominal ischaemia. 4. Intra-arterial (i.a.) injection of a high dose of IL-1beta (500 ng kg-1), but not of a lower dose (i.e. 15, 50 or 150 ng kg-1), stimulated most (six of seven) abdominal visceral afferents. 5. IL-1beta (15 ng kg-1, i.a.) significantly enhanced the increased activity of 11 of 13 C fibre afferents during 10 min of ischaemia. Conversely, an IL-1 type I receptor antagonist (IL-1ra, 1.5 microg kg-1, i.a.) significantly attenuated the increased activity in six of seven other C fibre afferents during ischaemia. 6. IL-1beta (15 ng kg-1, i.a.) significantly augmented the responses of 13 of 16 ischaemically sensitive abdominal afferents to histamine (5-10 microg kg-1, i.a.). Conversely, IL-1ra (1.5 microg kg-1, i.a.) significantly attenuated the responses of five of six other C fibre afferents to histamine. 7. These data strongly suggest that stimulation of IL-1 type I receptors by IL-1beta produced during brief abdominal ischaemia contributes to activation of visceral afferents during ischaemia, at least in part, by sensitizing the afferent nerve endings to ischaemia. Our data also show that exogenous IL-1beta sensitizes visceral afferents to histamine.