CALIXARENES WITH HOST-MEDIATED POTENCY IN EXPERIMENTAL TUBERCULOSIS -FURTHER EVIDENCE THAT MACROPHAGE LIPIDS ARE INVOLVED IN THEIR MECHANISM OF ACTION

Some time ago, it was found that attachment of hydrophilic polyoxyethy lene chains to various hydrophobic phenols and alcohols gave water-sol uble products which, although inactive in vitro, influenced an experim ental tuberculous infection. With short chains the infection was suppr essed, and with long chains it was promoted. Later work concentrated o n Macrocyclon (short chain) and HOC-60 (long chain), both derived from a hydrophobic, polyphenolic calixarene. Growth of Mycobacterium tuber culosis inside macrophages (M phi) was inhibited by Macrocyclon and st imulated by HOC-60. Also, triglyceride lipase from M phi extracts and an extracellular phospholipase were inhibited by M?lacrocyclon and sti mulated by HOC-60. This suggestion of a mechanism has been strengthene d by the finding that M phi cultivated in monolayers and treated with Macrocyclon showed accumulation of lipid and little formation of fatty acid after incubation of kilted cells. With HOC-60, lipid was deplete d and much fatty acid was found.