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Porphyrin and heme synthesis from endogenous and exogenous -aminolevulinic acid in Pseudomonas aeruginosa, Escherichia coli, and Achromobacter metalcaligenes was studied in growing cultures and in resuspended cells under moderately aerobic conditions. Similar investigations were also performed on A. metalcaligenes during the entire course of growth. Lactate served as the only source of energy for the growing and the resuspended cells; there was no supplementation with iron. Each of the three microorganisms synthesized from lactate all porphyrins with 8 to 2 carboxylic acid side chains, corresponding to the biosynthetic sequence. The relative amounts of porphyrins formed by Ps. aeruginosa, E. coli, and A. metalcaligenes are 5:1:1, and of heme 1:1.8:2.4. With exogenous -aminolevulinic acid theaminolevulinate synthase is bypassed, thus eliminating the latter's function as a regulatory ratelimiting enzyme. From lactate and ammonium

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Three exogenous pyrogens (Escherichia coli lipopolysaccharide, synthetic double-stranded ribonucleic acid. Newcastle disease virus) were compared with respect to their mechanisms of fever induction in rabbits. All inducers stimulated the production of an endogenous pyrogen demonstrated in the blood as well as prostaglandins of the E group, and of cyclic adenosine 3',5'-monophosphate in the cerebrospinal fluid. The concentrations of these compounds were elevated approximately twofold as compared to the controls. Independently of the mode of induction, the fever reaction could be prevented by pretreatment with 5 mg of cycloheximide per kg, although the three fever mediators were induced as in febrile animals. Consequently, at least one additional fever mediator that is sensitive to a 30 to 50% inhibition of protein synthesis by cycloheximide has to be postulated. The comparable reactions of the rabbits after administration of different pyrogens argues for a similar fever mechanism. In contrast to fever induction there was no stimulation of endogenous pyrogen, prostaglandins of the E group, and cyclic adenosine 3',5'-monophosphate in hyperthermia as a consequence of exposure of the animals to exogenous overheating. Furthermore, hyperthermia could not be prevented by cycloheximide.

In rabbit cerebrospinal fluid (CSF) during fever induced by endotoxins, myxoviruses, or endogenous pyrogen, concentrations of adenosine 3',5'-cyclic monophosphate (cyclic AMP) and prostaglandin E (PGE) are about 2-fold higher in comparison to normal values. In endotoxin treated animals paracetamol reduced the fever reaction and both PGE and cyclic AMP levels. Administration of theophyllin together with endotoxin enhanced the fever reaction and cyclic AMP levels in CSF, but had no influence on stimulation of PGE synthesis. Following injection of PGE2 into the lateral cerebral ventricles increased cyclic AMP concentrations were found in CSF. The results suggest, that the pyrogenic effect of PGE is mediated by stimulation of cerebral cyclic AMP synthesis.