Activation of complement by DMSO and ethanol and its inhibition by soluble complement receptor type 1.

The complement system is a series of serum proteins that perform cell lytic and pro-inflammatory functions as part of the bodies mechanism for removing foreign, dead or damaged cells. The complement system consists of the alternative and classical pathways. During activation the anaphylatoxins C4a and C3a are released and these can be measured using competitive MAS. Abherrant activation of the complement system has been implicated in a number of disease states e.g. acute lung injury, severe bums, myocardial injury and inflammatory diseases. During mechanistic studies on synthetic complement inhibitors it was observed that dimethyl sulfoxide (DMSO) was able to activate complement. This was an important observation because DMSO and other organic solvents are used routinely in phannaceutics and blood fractionation applications where complement activation is undesirable. This study explored the complement activation properties of DMSO and Ethanol, in human sera and was extended to include the use of recombinant human complement receptor type l(sCRl), a known complement inhibitor[l], to elucidate which complement pathways were involved. Human sera pooled from a screened panel of healthy volunteers was used in this study. Complement activation was monitored using a modified competitive RIA specific for C3a or C4a[2]. Undiluted serum samples were incubated for 60 mins at 37.C. and anaphylatoxin levels measured pre and post-incubation. Solvents used throughout this study were HPLC or ANALAR grade.