Cytotoxic Chemotherapy-Induced Changes in Plasma Mannan-Binding Lectin in Patients with Cancers.

Mannan-binding lectin (MBL) plays an important role in the innate immune responses in primates. The immune function of MBL is mediated by its ability to function as an opsonin and to activate complement through lectin pathway. Recently, there has been an interest in investigating the role of plasma MBL in patients undergoing chemotherapy for leukaemia. Reports indicate that low plasma MBL levels predispose to more severe and frequent infections. There is, however, no clear published data regarding the potential effect of cytotoxic drugs on plasma MBL levels in the absence of any overt sepsis. We conducted a study to obtain this information by carrying out serial measurements of plasma MBL levels during chemotherapy. In addition, we made serial assays of salivary MBL levels to ascertain whether changes in salivary content of this lectin during chemotherapy predispose to mucositis. Ten patients with various non-haematogenous malignancies receiving 3 weekly 5-fluouracil treatment were studied. Blood and saliva samples were collected prior to starting chemotherapy (baseline) and then before subsequent cycles of treatment. ‘Normal range’ of plasma MBL was established by measuring 50 plasma samples obtained from healthy blood donors. Plasma MBL was measured by an ELISA technique using mouse monoclonal antibody IgG1 anti MBL. Salivary MBL level was measured by a modified technique using the same antibody. The results show that there is a marked variation in the plasma MBL levels in healthy individuals (11ng/ml- 9189ng/ml, with a mean of 3057ng/ml). Similarly, the plasma MBL levels of the patient cohort also showed marked variation (10ng/ml- 10896ng/ml with a mean of 3243ng/ml). However, within an individual patient the plasma MBL level rose markedly following first course of chemotherapy. The mean post-first dose rise was 59.2%. Nine out of ten patients exhibited this phenomenon. Interestingly, however, the changes in plasma MBL levels with subsequent treatments were more varied ie in some patients (3/10) the levels continued to rise while in others the levels decreased. Salivary MBL levels in all patients were below detection limit suggesting that polymeric MBL is not present in significant quantities in saliva. Based on the findings of this study we conclude that cytotoxic drugs such as 5-FU may cause significant changes in plasma MBL levels and, therefore, caution should be exercised in interpreting individual measurements following chemotherapy when making any correlation between post chemotherapy plasma MBL levels and infection risk.