Summary Eighteen patients with advanced cancer have been treated intravenously with human recombinant tumour necrosis factor (rhTNF). The drug produced febrile reactions at all doses although these were preventable by steroids and indomethacin. Doses at or above 9 x 105 units (400 pg)m-2 were associated with hypotension, abnormal liver enzymes, leucopenia and mild renal impairment in a substantial proportion of patients. RhTNF was cleared from plasma with a half life of -20 minutes but non-linear pharmacokinetics were seen with decreased clearance at higher doses. In 3 patients, all with lymphoma, improvements in their tumours were recorded.RhTNF was noted to produce rapid increases in serum C-reactive protein concentrations. Endogenous TNF levels were not found to be elevated in 72 cancer patients.TNF deserves further therapeutic evaluation and these observations support its biological importance as an endogenous pyrogen, mediator of acute phase protein responses, and a mediator of endotoxic shock.

SUMMARY Biologically active tumour necrosis factor (TNF) was detected in medium conditioned by incubation with cxplants of human pregnancy decidua or fetal chorionic villous tissue, taken in the first trimester and at term. Addition of endotoxin increased TNF release in most cases. ELISA assays gave similar results for TNF–α and also demonstrated low levels of TNF–β. Using cell populations purified by flow cytometry, secretion of biologically active TNF was shown to be localized to the macrophages. Cytotrophoblast purified from term amniochorion produced no TNF. Both decidual and chorionic villous tissue at term contained mRNA for TNF–α and TNF–β. TNF–α mRNA was confined to decidual macrophages in first trimester tissue, and was not present in chorionic cytolrophoblast. TNF–β mRNA, in contrast, was detected in both macrophage and no‐acrophage populations in term dccidua.

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Circulating levels of SP, were measured in 20 insulin dependent diabetic women during the third trimester of pregnancy. With one exception, SP, levels were between the 80 per cent confidence limits of the normal range. The exception was a patient who was delivered of a normal infant at 37 weeks but had consistently low levels of SP, from 32 weeks until delivery, suggesting a specific defect in SP, synthesis.PREGNANCY specific ( 3, glycoprotein (SP,) is one of a new generation of proteins recently isolated from late pregnancy blood (Tatarinov and Masyukevich, 1970) and placenta (BQhn, 1971). The clinical application of SP, measurement in the maternal circulation as an index of fetal wellbeing has been reviewed (Chard and Grudzinskas, 1979;Horne and Towler, 1979). The biological function of SP, during pregnancy is unknown although minor fluctuations in circulating levels of SP, after induced hypo-and hyperglycaemia (Tatra et al, 1976) have sug-Present addresses