In this report, we have examined the mechanism of action of Inmunoferon(R), a patented glycoconjugate (GC) of natural origin with immunomodulatory properties, in the regulation of TNF-α expression induced by LPS challenge in a rodent model. GC was found to be dependent on a normal HPA response to exert its regulatory effect on TNF-α expression. Adrenalectomized mice were unresponsive to the drug in terms of TNF-α levels after LPS challenge, whereas control mice showed lower serum TNF-α levels when treated with GC than vehicle-treated animals. GC treatment also induced the expression of acute phase proteins but it did not alter the normal metabolism or viability of hepatic cells. These data suggested the employment of GC as a novel adjuvant during antibacterial treatment without disadvantages such as side effects in the metabolism of the liver, thus, acting as an enhancer of the host response against infection.