Effects of antibiotics on the active oxygen production by neutrophils in the primary host-defense mechanism.

1995 Fiscal Year Final Research Report Summary

• Project/Area Number: 05671653
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: HIROSAKI UNIVERSITY
• Principal Investigator: FUKUI Roh HIROSAKI UNIVERSITY,SCHOOL OF MEDICINE,INSTRUCTOR, 医学部, 助手 (70241479)
• Project Period (FY): 1993 – 1995
• Keywords: Antibiotics / Neutrophls / Superoxide anion radical / Primary host-defense mechanism

Research Abstract

Almost all diseases infected with bacteria were treated by antibiotics, however, we often experienced some kinds of antibiotics showed no effects for an infectious disease occurred in compromised host such as an end-stage of cancer patient or an advanced aged person. The active oxygen species produced by neutrophils were known to be key molecule, which play an bactericidal role in the primary defense of human body against infection. But the interaction between the antibiotics and the function of neutrophils, especially the production of an active oxygen, was not well understood. Therefore, the author investigated the effects of antibiotics on superoxide anion radical (0_2^<・->) production by human neutrophils and 0_2^<・-> production by neutrophils in peripheral blood of volunteers and patients with oral cancer or osteomyelitis of the mandible. The assay of 0_2^<・-> production in stimulated neutrophils or hypoxanthine-xanthine oxidase (HX-XOD) system was performed by CLA-dependent chemi luminescence method and the assay of hydroxyl radical (HO^・) generation system was performed by ESR spin trapping technique.
The results were as follows ;
1.When neutrophils were stimulated by opsonized zymozan, seven antibiotics enhanced 0_2^<・-> production and when stimulated by PMA,six antibiotics enhanced that. In HX-XOD reaction systen, three antibiotics enhanced 0_2^<・-> generation and other three antibiotics suppressed that. However, no antibiotics influenced HO^<・-> generation. 2.0_2^<・-> production by neutrophils from the peripheral blood of patients with above described diseases were lower than of healthy volunteers. Especially, 0_2^<・->production by neutrophils of oral cancer patients with MRSA infection are lower than the other patients. 3.These findings revealed that the primary host-defense mechanism were suppressed in such patients as were accompanied with severe infectious diseases in oral and maxillofacial regions.
These results suggested that 0_2^<・-> production by neutrophils were responsible for the primary host-defense mechanism. Furthermore, to select the antibiotic according to the ability, which enhanced 0_2^<・-> production or not, was necessary for the treatment of patients with severe infection disease.