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We studied changes of humoral immunity, such as complement pathway activity, C3 contents and contents of immunoglobulin, in mice injected subcutaneously with BeCl2 or CuCl2 once a week for 12 weeks. Mean body weights of JCL: ICR female mice were approximately 30g in control mice (control group; n = 7), in mice injected with Be (Be group; n = 8) and in mice injected with Cu (Cu group; n = 8). Values of classical complement pathway activity (CH50) were 18.8 +/- 1.4 U per ml, 15.3 +/- 1.8 U per ml and 16.7 +/- 1.3 U per ml in the control group, Be group and Cu group, respectively. The CH50 values of Be and Cu groups were significantly lower than that of the control group (P < 0.01). In contrast, values of alternative complement pathway activity (ACH50) and contents of C3 were almost constant in the three groups. The immunoglobulin content in the Be group tended to increase. The activity of alanine aminotransferase in the Be group was markedly higher than that in the control group (P < 0.05), and the aspartate aminotransferase activity was also high. The CH50 value of mice injected with a small amount of Be once a week over a 12-week period decreased markedly, although either the ACH50 value or C3 content was the same as in the control group. The immunoglobulin content somewhat increased in the Be group. These results suggest the possibility that immune complex is induced by Be.

Complement system was investigated in 7 patients with status asthmatics treated with large doses of methylprednisolone (MPS). Complement hemolytic activities, complement protein profile, complement fragments and circulating immune complexes were measured before, 3 and 8 hours after and 14 days after MPS administration. MPS normalized C4 and C1INH activities 6 hours after administration. MPS also decreased ACH50 6 hours after administration and D activity 3 and 6 hours after, but these activities recovered to their previous normal range within 14 days. P and H were decreased at each measurement time, and C1s was transiently decreased 6 hours after MPS administration. Complement fragment iC3b was increased at each measurement time, but fragment Bb tended to be decreased 14 days after MPS administration. The increment of anaphylatoxin C3a recovered to normal 14 days after MPS administration. In vitro experiments, MPS inhibited D and C1s activation directly, and decreased the decay of B and C4. Inhibition of C1s might also increase C1INH activity clinically. These results clarified that the alternative complement pathway was activated, and suggested that the C1 bypass pathway might be also activated in status asthmatics. It was further considered that these anti-complementary effects induced by MPS, brought about an improvement in asthmatic symptoms. Studies to identify the complement activators continued, and circulating immune complexes may possibly be one of those agents activating complement cascade.

Lentinan, a pure polysaccharide, augments many immune responses in vivo but not in vitro. Therefore reaction with any factor is thought to be required for triggering of immunopotentiation by lentinan. To clarify the role of complement in this effect, we investigated whether lentinan could activate alternative pathway of complement or not and the relation with the immunopotentiation in 13 gastric cancer patients. C3, C3a, C5 and C5a levels as parameters of complement activation and interleukin-2 producing activity as parameter of immunopotentiation were assayed before and immediately after intravenous injection of lentinan. Among these complement components, remarkable change was observed only in C3a level. C3a level elevated to more than 1000ng/ml from less than 300ng/ml. And according to the degree and continuation of the elevation, these patients were classified into 3 types-(1) every time little elevation, (2) first remarkable and thereafter little elevation and (3) continuous remarkable elevation. Such an elevated C3a level returned to the level before lentinan injection within one day. When C3a level elevated to more than 1000ng/ml, leukocyte counts of peripheral blood decreased significantly and interleukin-2 producing activity increased concomitantly. Thus, there was diversity in response to lentinan and complement activation was suggested to have contribution in immunopotentiation by lentinan.