Helminthic therapy and eosinophils
What are eosinophils?
Eosinophils, sometimes called eosinophiles, eosinocytes, or less commonly, acidophils or acidophilic leukocytes, are a variety of white blood cells and one of the immune system components responsible for combatting multicellular parasites and certain infections in vertebrates. Along with mast cells and basophils, they also control mechanisms associated with allergy and asthma. [1]
The positive role of eosinophils
Eosinophil numbers usually increase following exposure to helminths, but this is not an undesirable development. The interactions between eosinophils and intestinal worms are now recognised to be complex and, rather than being detrimental, eosinophils may in fact be an essential component in immunity. They have an important role in cell growth and cell-to-cell interactions. They synthesise, store and secrete cytokines, chemokines, and growth factors, as well as stimulating T cells, interacting with B cells, functioning as antigen-presenting cells, and regulating processes associated with both T1 and T2 immunity. [2] They also perform many other essential biological functions.
One of the contributions made to immune regulation by eosinophils is the production of the cytokine Interleukin-5 (II-5 cytokine) which induces the body’s T-cell front-line defences and has, itself, been shown to be an effective treatment for autoimmune disease. [4] Eosinophils may act as mediators of inflammatory resolution, [5] have a crucial role in the prevention of autoimmune diseases such as colitis, [6] and contribute to the control of excessive inflammation and tissue damage in solid organ transplants. [7]
Small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis, [8] including by the regulation of Th17 cells via production of IL-1Ra. [9]
Hookworm-induced eosinophils may contribute to a reduced prevalence of latent TB infection. [10]
An absence of eosinophils may have a significant impact on the nature of the endogenous gut microflora and responses to gut pathogens, notably Clostridium difficile. [11]
The eosinophil response to helminths
In the case of helminth infection, eosinophils are produced by the body to try to rid itself of the invader. The helminths then respond by secreting chemicals to counter the eosinophils and thus protect themselves from being ejected. This produces a typical pattern of firstly increased, and then decreased, eosinophil counts. However, there is not always an eosinophil response to helminths.
Raised eosinophil numbers should always be investigated because they can be a sign of pathology other than a reaction to an allergen or parasite.
Where eosinophil levels had been raised prior to inoculation with helminths, for example in response to harmless substances such as food proteins, these will typically also be controlled eventually by the action of the worms. Once helminths have been hosted continuously for a period of time, eosinophil numbers usually decline and can eventually disappear with chronic helminth exposure, although they usually remain slightly elevated indefinitely in helminth hosts.
Eosinophil levels vary according to the species and number of helminths being hosted, and the genetics of the host. In the case of NA, they usually begin to rise from week 2 following inoculation, then rise more rapidly from week 4 and peak at around weeks 6-7, before reducing gradually again and returning to normal at around 14 weeks, or remaining slightly elevated thereafter. The lower eosinophil levels seen at 14 weeks and beyond are an indication that the worms are doing their job and moderating the body's immune response.
(From: Dose-ranging study for trials of therapeutic infection with Necator americanus in humans)
Measurement scales vary according to geographic location, and someone from the US reported that, after his first inoculation with hookworms, his eosinophil counts rose from a baseline of about 300 to a peak of 4100 at 5 weeks, dropped to 2300 at 12 weeks, and then reduced to 1300 at 14 weeks. After a 2nd inoculation, his eosinophils rose to 2300 at week 8, dropped back to 2100 at week 12, and then down to 1300 at week 14. Following a 3rd inoculation, his eosinophils reached 1700 at 7 weeks before falling to 600 at week 11.
Someone else has reported that, eight months before introducing NA, they had an eosinophil level of 300/mm3. Nine weeks after their first dose of NA (and while also taking HDC), their eosinophils had increased to 2449/mm3 and, by 22 weeks, they had reduced to 1360/mm3. At almost 15 weeks after a second dose, their eosinophils had risen back up to 2900/mm3. [16]
An eosinophil count of, say, 600, prior to infection with helminths, might be indicative of allergies, but counts in the thousands are more suggestive of the presence of helminths. However, a high eosinophil level does not necessarily indicate that a person is currently infected with helminths, only that they may have been exposed to helminths within the last few weeks or months.
Having an eosinophil level somewhat elevated above 'normal' values does not automatically lead to adverse symptoms.
And the increase in eosinophil counts seen in helminth hosts is no reason for concern.
Once human helminths (NA or TT) have been established for three months, the immune response to them, whether to those already in place, or to supplementary doses, is reduced and, the larger the number of worms being hosted, the smaller the resulting rise in eosinophils will be. This is probably the reason why one study found that, out of a total of 621 cases of helminth infection, only 66 cases (10.6%) had related eosinophilia. [20]
This is also why side effects - which are dependent on the host’s immune response - are much less likely and, if they do occur, are so much milder, with subsequent doses when compared with the first dose.
One self-treater, whose eosinophil numbers had always been in the normal range prior to hosting helminths, found that they rose appropriately during several years of hosing NA. But, when he then took a break from the therapy for 3 years, his eosinophil count continued to remain outside the upper limit of normal. [21]
See also