Can Kupffer cells influence the development of liver metastases? A clinical and experimental study.

A review of the historical background, structure, functions, turnover, opsonins and interaction in immune mechanisms of Kupffer cells is made. Theories of tumour spread, in particular blood borne metastases are discussed followed by the limited data of Kupffer cell function in neoplasia. The methods used in rats are described, in particular the development of techniques of (i) assessing Kupffer cell function: (ii) altering Kupffer cell function; (iii) measuring plasma fibronectin and C-reactive protein levels and (iv) a tumour model which produces liver metastases. It also describes the method of Kupffer cell assessment and the measurement of plasma fibronectin and other opsonins in patients. The Results Section contains the results of the clinical studies followed by the results of the animal studies. The clinical studies fail to demonstrate that surgery produces a change in Kupffer cell function, in particular Kupffer cell depression. The results however are inconclusive because of technical problems. They also show that patients with neoplastic conditions usually have normal plasma fibronectin levels. The animal experiments show that one tumour produced Kupffer cell stimulation whereas another did not. This is discussed. Neoplasia was found to have no effect on rat plasma fibronectin levels or C-reactive protein levels. Kupffer cell stimulation in animals prior to being injected with tumour cells caused a marked reduction in the number of liver metastases subsequently growing. The converse was true of Kupffer depression. It is concluded that Kupffer cells in this model can influence the development of liver metastases and its relevance is discussed.