This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by McBride, W. T. Articles by Armstrong, M. Search for Related Content PubMed PubMed Citation Articles by McBride, W. T. Articles by Armstrong, M.

---

LETTERS TO THE EDITOR

Clomethiazole Alters Immune Function Within an Isolated Cardiopulmonary Bypass Circuit

Department of Anesthesia, Royal Victoria Hospital, Belfast, Northern Ireland Department of Microbiology and Immunobiology, Queen’s University, Belfast, Northern Ireland

To the Editor:

Harmon et al. (1) showed that clomethiazole in an isolated cardiopulmonary bypass (CPB) system (n = 5) significantly reduced IL-8, TNF-, and IL-6. Neutrophil CD18 did not increase in either control or clomethiazole circuits, but after 120 min was lower with clomethiazole. The authors suggest that expression of CD18 reflects the whole family of ß₂ integrins. This was not our experience. In a similar system (n = 10) CD18 did not increase significantly but CD11b did (2). Therefore, CD11b is a particularly useful marker in determining neutrophil inflammatory responses during isolated CPB. Although this CD11b response is consistent with the in vivo response (3), we still recommend caution when extrapolating from in vitro to in vivo. For example, methylprednisolone-mediated reduction in neutrophil CD11b expression observed at in vivo CPB (4) was not repeated in isolated CPB (2), even though methylprednisolone reduced plasma IL-8 in the isolated circuit (2).

Drugs may exert antiinflammatory effects by several mechanisms that may require a functioning antiinflammatory response.

Isolated CPB cannot generate a plasma antiinflammatory cytokine response (2,3,5). Accordingly, this system only identifies a test drug’s ability to directly reduce the proinflammatory response independent of the antiinflammatory response. This limitation needs to be considered in interpreting the results of Harmon et al. with clomethiazole.

References

1. Harmon D, Coleman E, Marshall C, et al. The effect of clomethiazole on plasma concentrations of interleukin-6, -8, -1ß, tumor necrosis factor-, and neutrophil adhesion molecule expression during experimental extracorporeal circulation. Anesth Analg 2003; 97: 13–8.[Abstract/Free Full Text]
2. Gormley SM, Armstrong MA, McMurray TJ, McBride WT. The effect of methylprednisolone on cytokine concentration and leukocyte adhesion molecule expression in an isolated cardiopulmonary bypass system. Cytokine 2003; 22: 149–55.[Web of Science][Medline]
3. McBride WT, Armstrong MA, Crockard AD, et al. Cytokine balance and immunosuppressive changes at cardiac surgery: contrasting response between patients and isolated CPB circuits. Br J Anaesth 1995; 75: 724–33.[Abstract/Free Full Text]
4. Hill GE, Alonso A, Thiele GM, Robbins RA. Glucocorticoids blunt neutrophil CD11b surface glycoprotein upregulation during cardiopulmonary bypass in humans. Anesth Analg 1994; 79: 23–7.[Abstract/Free Full Text]
5. Bedi A, McBride WT, Armstrong MA, et al. Xenon has no effect on cytokine balance and adhesion molecule expression within an isolated cardiopulmonary bypass system. Br J Anaesth 2002; 89: 546–50.[Abstract/Free Full Text]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by McBride, W. T. Articles by Armstrong, M. Search for Related Content PubMed PubMed Citation Articles by McBride, W. T. Articles by Armstrong, M.