Anti-HIV
activity by MGN-3 In Vitro
Human
immunodeficiency virus (HIV) is the causative agent of the acquired immunodeficiency
syndrome (AIDS). HIV is one of the principle threats of human life and
health worldwide. According to several sources (Center for Disease Control,
AIDS hot line, Red Cross and public health sources) there are approximately
1.5 million HIV infected people in the United States and many millions
worldwide. It has been estimated that by the year 2000 approximately 110
million will be infected with HIV (2% of the world population). Drugs such
as AZT, have been developed as treatments for AIDS.
However
they have significant side effects and have questionable effectiveness.
Furthermore, the emergency of HIV strains resistant to AZT and other nucleoside
analogues poses a major hindrance to slow down the AIDS disease progression.
At
the last international conference held in Japan, there was very little
promise of a vaccine in the next five years. The lack of vaccine or satisfactory
treatment makes this disease uniquely alarming. Therefore, currently there
is much interest and need to identify anti- HIV agents that are not only
active against the virus but also can potentiate host immune system.
MGN-3
is a natural biological response modifier (BRM)
MGN-3 is an extract of arabinoxylane from rice bran; has been treated
enzymatically with an extract from Hyphomycetes mycelia. It is polysaccharides
that contain B-1.4 xylopyranose hemicellulose. MGN-3 was offered by Daiwa
Pharmaceutical Co.,
1.
MGN-3:
MGN-3
is an arabinoxylane from rice bran that been enzymatically modified by
Hyphomycetes mycelia.
2.
Patients
:
5
HIV patients were participated in the study, 20 cc blood was drawn from
each patient.
3.
PBL
Mononuclear
cells from the subjects were separated from the fresh whole blood by Ficoll-hypaque
density gradient centrifugation ( Litton Biogenetics, Rockville, MD).
The
lymphocyte band at the interface was collected and cells pelleted by centrifugation,
washed twice in RPMI-1640, supplemented with 10% ( v/v) fetal calf serum,
2 mM glutamine, 25mM Hepes ( PH 7.2), 50 units penicillin and 50 µg
streptomycin per ml ( Grand Island Biologicals, Santa Clara, CA. )
4.
Syncytia Formation studies:
Peripheral
Blood Lymphocytes (PBL) from AIDS patients were cultured with PHA in the
presence or absence of different concentrations of MGN-3 (12.5-100 ug/mi)
for 7 days.
The
number of syncytia were evaluated, and the size of each was also recorded.
The effect of MGN-3 on PHA induced PBL proliferation was studied by MTT
assay.
Treatment
with MGN-3 resulted in:
1-
Significant inhibition in the SF
2-
The effect was dose dependent, percentage of inhibition in SF was 38.5,
50,62.5, and 75% at concentration of 12.5, 25, 50, and 100ug/ml respectively,
Fig.
1 .
3-
Complete absence of SF having large and medium size post treatment,
Table
1.
4-MGN-3
caused25-30% inhibition of PBL proliferation, Fig
2.
5-
Increase NK cell activity in vitro, Fig.
3
We
concluded that MGN-3 is a natural product that dose not have side effects.
It possesses:
I
-potent effect against syncytia formation by HIV.
2-Immunomodulatory
function for NK cell and IFN- y production.
These
properties of MGN-3 may be of potential value in therapy of HIV infection.