Hookworms, anemia, autoimmunity and the HIF-1/EPO/cathelicidin pathway induced by iron deficiency

Recently published research shows that hyrdoxylase inhibitors have
gastroprotective properties through the induction of HIF-1a, thus making
them a potential medication for leaky gut problems [PMID 18166353,
18166352]. Low iron conditions and iron chelators like EGCG also
activate HIF-1a, as does cobalt chloride as I pointed out in another
post.

I was reviewing my notes on autoimmunity and a connection became very
clear. Intestinal helminths block the development of autoimmunity and
allergy. A medical researcher at the University of Nottingham named
Alan Brown took hookworms to cure his allergies several years ago and he
mentioned their only drawback was that they caused mild anemia
<http://www.cosmosmagazine.com/node/695> - in other words, iron
deficiency. It didn't occur to me that these linked up until now. I
believe that this anemia could actually be central to the
gastroprotective role of helminths. The hookworms could trip HIF-1a via
low iron just like iron chelators do thus performing the job of the
hydroxylase inhibitors used in the recent leaky gut research.

Cathelicidin is downstream of vitamin D3/HIF-1a and tilts mast cell
inflammation towards innate immunity [PMID 18239275] and away from the
spontaneous degranulation seen in allergy and other autoimmune
conditions. This HIF-1a pathway also induces angiogenesis in the skin
[PMID 17536272] and I think it might behave similarly in the gut.
Defects in the HIF-1a pathway might then account for the deranged
angiogenesis we see in certain inflammatory bowel conditions.

On 4/13/08 8:11 PM, in article
kofi-23C12E.22110613042008@news.east.earthlink.net, "Kofi" <kofi@anon.un>
wrote:

> Recently published research shows that hyrdoxylase inhibitors have
> gastroprotective properties through the induction of HIF-1a, thus making
> them a potential medication for leaky gut problems [PMID 18166353,
> 18166352]. Low iron conditions and iron chelators like EGCG also
> activate HIF-1a, as does cobalt chloride as I pointed out in another
> post.
>
> I was reviewing my notes on autoimmunity and a connection became very
> clear. Intestinal helminths block the development of autoimmunity and
> allergy. A medical researcher at the University of Nottingham named
> Alan Brown took hookworms to cure his allergies several years ago and he
> mentioned their only drawback was that they caused mild anemia
> <http://www.cosmosmagazine.com/node/695> - in other words, iron
> deficiency. It didn't occur to me that these linked up until now. I
> believe that this anemia could actually be central to the
> gastroprotective role of helminths. The hookworms could trip HIF-1a via
> low iron just like iron chelators do thus performing the job of the
> hydroxylase inhibitors used in the recent leaky gut research.
>
> Cathelicidin is downstream of vitamin D3/HIF-1a and tilts mast cell
> inflammation towards innate immunity [PMID 18239275] and away from the
> spontaneous degranulation seen in allergy and other autoimmune
> conditions. This HIF-1a pathway also induces angiogenesis in the skin
> [PMID 17536272] and I think it might behave similarly in the gut.
> Defects in the HIF-1a pathway might then account for the deranged
> angiogenesis we see in certain inflammatory bowel conditions.

That's why there is little asthma in the Sudan - very high incidence of GI
worms.
Theory is more that the entire allergy system is designed originally for
worm protection so if the immune system is busy with the worms, not much
left over for Asthma.